The fate of the oculomotor system in clinical bilateral anophthalmia

AbstractThe interdependence of the development of the eye and oculomotor system during embryogenesis is currently unclear. The occurrence of clinical anophthalmia, where the globe fails to develop, permits us to study the effects this has on the development of the complex neuromuscular system controlling eye movements. In this study, we use very high-resolution T2-weighted imaging in five anophthalmic subjects to visualize the extraocular muscles and the cranial nerves that innervate them. The subjects differed in the presence or absence of the optic nerve, the abducens nerve, and the extraocular muscles, reflecting differences in the underlying disruption to the eye’s morphogenetic pathway. The oculomotor nerve was present in all anophthalmic subjects and only slightly reduced in size compared to measurements in sighted controls. As might be expected, the presence of rudimentary eye-like structures in the socket appeared to correlate with development and persistence of the extraocular muscles in some cases. Our study supports in part the concept of an initial independence of muscle development, with its maintenance subject to the presence of these eye-like structures.

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The Extraocular Muscles and Diplopia

Eye Movement Disorders in Clinical Practice ◽

10.1093/med/9780199921805.003.0004 ◽

2014 ◽

pp. 124-161

Author(s):

Shirley H. Wray ◽

Shirley H. Wray

Keyword(s):

Eye Movements ◽

Nerve Palsy ◽

Neuromuscular Junctions ◽

Cranial Nerves ◽

Abducens Nerve ◽

Extraocular Muscles ◽

Oblique Muscle ◽

Oculomotor Nerve Palsy ◽

Subjective Complaint ◽

Oculomotor Nuclei

deals with action and innervation of the extraocular muscles. In their intact state, the extraocular muscles and the cranial nerves that innervate them are responsible for every movement of the eyes signaled by the cortex. Diplopia, or double vision, is the commonest subjective complaint associated with a lesion affecting the extraocular muscles, their neuromuscular junctions, the oculomotor nuclei or nerve, or pathways in the brainstem that maintain alignment of the eyes. The diplopia history focuses on distinguishing monocular from binocular diplopia and the diplopia examination pays attention to head position, ocular alignment, and the range of eye movements during monocular and binocular viewing as keys to diagnosis. Diplopia with full eye movements is fully discussed. Four illustrative cases are presented: episodic diplopia due to ocular myasthenia gravis; a case of esotropia (paresis of the lateral rectus with inward deviation of the eye) due to an abducens nerve palsy; a case of exotropia (paresis of the medial rectus with outward deviation of the eye) due to a fascicular oculomotor nerve palsy; and a case of hypertropia (vertical misalignment of the eyes due to paresis of the superior oblique muscle vs. skew deviation) caused by a post-traumatic trochlear nerve palsy.

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Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans

Human Molecular Genetics ◽

10.1093/hmg/ddz137 ◽

2019 ◽

Vol 28 (18) ◽

pp. 3113-3125 ◽

Cited By ~ 2

Author(s):

Mary C Whitman ◽

Noriko Miyake ◽

Elaine H Nguyen ◽

Jessica L Bell ◽

Paola M Matos Ruiz ◽

...

Keyword(s):

Chemokine Receptor ◽

Ex Vivo ◽

Involuntary Movement ◽

Scavenger Receptor ◽

Abducens Nerve ◽

Missense Variant ◽

Oculomotor System ◽

Oculomotor Nerve ◽

Cxcr4 Signaling ◽

Duane Syndrome

Abstract Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.

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Histogenesis of Human Extraocular Muscles and Its Innervation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080250 ◽

1977 ◽

Vol 35 ◽

pp. 564-565

Author(s):

A. Julio Martinez ◽

M. Barmada

Keyword(s):

Electron Microscopy ◽

Gestational Age ◽

Light And Electron Microscopy ◽

Abducens Nerve ◽

Extraocular Muscles ◽

Oculomotor Nerve ◽

Paraxial Mesoderm ◽

Optic Vesicle ◽

Trochlear Nerve ◽

Embryonic Myogenesis

Embryonic myogenesis and neurogenesis of human extraocular muscles (EOM) were studied by light and electron microscopy in a group of embryos and fetal specimens (6 to 24 weeks gestational age) (20 to 200 mm CR length).The earliest trace of EOM in humans have been reported at 7 mm (4 weeks) as a single undifferentiated mass of condensed paraxial mesoderm surrounding the optic vesicle. There is no separation between individual muscles. The distinction occurs before the 20 mm stage (6-7 weeks) when the 4 recti and the 2 obliques can be recognized(1). The oculomotor nerve can be identified as an elongation of the midbrain at 12.2 mm (5th week). The trochlear nerve appears between the 6th and 7th weeks and the abducens nerve is recognizable first at 31.3 mm (8th week). By the end of the 8th week, all the nerves had reached their respective muscles.

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Botox’s Place in the Complex Treatment of Oculomotor System Pathology (the Optimal “Portrait” of the Patient for the Chemodenervation)

Ophthalmology in Russia ◽

10.18008/1816-5095-2018-2s-261-267 ◽

2018 ◽

Vol 15 (2S) ◽

pp. 261-267

Author(s):

I. L. Plisov ◽

V. V. Cherhykh ◽

V. V. Atamanov ◽

N. G. Antsiferova ◽

V. B. Pushchina ◽

...

Keyword(s):

Optimal Algorithm ◽

Cranial Nerves ◽

Optimal Dose ◽

Functional Results ◽

Oculomotor System ◽

Extraocular Muscles ◽

Alternative Methods ◽

Complex Treatment ◽

Patients Âgés ◽

Results Of Treatment

Introduction. To summarize our fifteen-years clinical experience of using Botox in strabismology and determine the indications for the most effective use of chemodenervation in the complex treatment of oculomotor system pathology.Patients and methods. To carry out chemodenervation of extraocular muscles, Botox was used. The optimal dose of Botox for intramuscular injection ranged from 1.25 to 5.0 units. The choice of dosage depends on the patient’s age, the type oculomotor system pathology, the level of muscular dysfunction and the purpose of the treatment. The treatment was performed in 376 patients with various disorders of oculomotor system. At the time of treatment, the patients’ ages ranged from 12 to 78 years. Injection of Botox into the extraocular muscles in all cases was the primary method of treatment.Results. In general, the state of relative functional recovery was achieved in 71.81% of cases (in 270 patients). The best results were obtained in treatment of decompensated heterophories, acute heterotrophies, atypical heterotrophies and primary hyperfunction of the inferior oblique muscles (in 100% of cases). In these conditions, the binocular vision was preserved in patients, and the imbalance of the oculomotor system did not show any sign of incomitance. However, patients with paralysis and paresis of the cranial nerves chemodenervation allowed creating conditions for a more complete restoration of muscular functions, to avoid the occurrence of a secondary imbalance in the oculomotor system. In 70.3% cases (185 patients), subsequent surgical treatment was not required. Reliable functional results of treatment allowed creating the optimal algorithm for chemodenervation.Discussion. Chemodenervation of extraocular muscles is an effective independent and additional method of complex treatment of oculomotor system pathology and expands opportunities in patients’ rehabilitation. To achieve maximum functional results, it is necessary to select patients correctly for this procedure, taking into account its appropriateness and advantages over alternative methods of treatment, selection of optimal dosages of Botox.

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Morphometry of the Oculomotor Nerve in Duane’s Retraction Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm9061983 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1983 ◽

Cited By ~ 1

Author(s):

Min Seok Kang ◽

Hee Kyung Yang ◽

Jounghan Kim ◽

Jae Hyoung Kim ◽

Jeong-Min Hwang

Keyword(s):

High Resolution ◽

Rectus Muscle ◽

Abducens Nerve ◽

Oculomotor Nerve ◽

Mri Findings ◽

Affected Side ◽

Retraction Syndrome ◽

Duane’S Retraction Syndrome ◽

Magnetic Resonance Imaging Mri ◽

Present Group

Objective: To investigate the morphometric characteristics of the oculomotor nerve and its association with horizontal rectus muscle volume in patients with Duane’s retraction syndrome (DRS) according to the presence of the abducens nerve. Methods: Fifty patients diagnosed with unilateral DRS were divided into two groups according to high-resolution magnetic resonance imaging (MRI) findings; DRS without an abducens nerve on the affected side (absent group, n = 41), and DRS with symmetric abducens nerves on both sides (present group, n = 9). Oculomotor nerve diameter was measured on high-resolution MRI in the middle of the cisternal space. The medial rectus muscle (MR) and lateral rectus muscle (LR) volumes were measured on T2-weighted coronal MRI of the orbit. Associations of oculomotor nerve diameter and horizontal rectus muscle volumes were performed according to the presence and absence of the abducens nerve. Results: Oculomotor nerve diameter on the affected side was thicker than that of the non-affected side in the absent group (p < 0.001), but not in the present group (p = 0.623). In the absent group, there was a positive correlation between oculomotor nerve diameter and MR volume (r = 0.779, p < 0.001), as well as the LR volume (r = 668, p = 0.023) of the affected eye. Conclusions: In DRS patients with an absent abducens nerve, the oculomotor nerve diameter was thicker in the affected eye compared to the non-affected eye. Oculomotor nerve diameter was associated with MR and LR volumes in the absent group. This study provides structural correlates of aberrant innervation of the oculomotor nerve in DRS patients.

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Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles

International Journal of Molecular Sciences ◽

10.3390/ijms22052575 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2575

Author(s):

Mervyn G. Thomas ◽

Gail D. E. Maconachie ◽

Helen J. Kuht ◽

Wai-Man Chan ◽

Viral Sheth ◽

...

Keyword(s):

Optic Nerve ◽

Retinal Ganglion Cells ◽

Optic Nerve Head ◽

Ganglion Cells ◽

Cranial Nerves ◽

Extraocular Muscles ◽

Missense Mutations ◽

Retinal Ganglion ◽

Fiber Layer ◽

Congenital Fibrosis

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p < 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.

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Very High Resolution Analysis of the Dynamics of a Coronal Plasmoid

International Astronomical Union Colloquium ◽

10.1017/s0252921100026117 ◽

1994 ◽

Vol 144 ◽

pp. 593-596

Author(s):

O. Bouchard ◽

S. Koutchmy ◽

L. November ◽

J.-C. Vial ◽

J. B. Zirker

Keyword(s):

High Resolution ◽

Solar Eclipse ◽

Total Solar Eclipse ◽

Field Of View ◽

Small Field ◽

High Resolution Analysis ◽

Ccd Observations ◽

Resolution Analysis ◽

Very High ◽

Small Field Of View

AbstractWe present the results of the analysis of a movie taken over a small field of view in the intermediate corona at a spatial resolution of 0.5“, a temporal resolution of 1 s and a spectral passband of 7 nm. These CCD observations were made at the prime focus of the 3.6 m aperture CFHT telescope during the 1991 total solar eclipse.

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