Functional characterization of orbicularis oculi and extraocular muscles

The orbicularis oculi are the sphincter muscles of the eyelids and are involved in modulating facial expression. They differ from both limb and extraocular muscles (EOMs) in their histology and biochemistry. Weakness of the orbicularis oculi muscles is a feature of neuromuscular disorders affecting the neuromuscular junction, and weakness of facial muscles and ptosis have also been described in patients with mutations in the ryanodine receptor gene. Here, we investigate human orbicularis oculi muscles and find that they are functionally more similar to quadriceps than to EOMs in terms of excitation-contraction coupling components. In particular, they do not express the cardiac isoform of the dihydropyridine receptor, which we find to be highly expressed in EOMs where it is likely responsible for the large depolarization-induced calcium influx. We further show that human orbicularis oculi and EOMs express high levels of utrophin and low levels of dystrophin, whereas quadriceps express dystrophin and low levels of utrophin. The results of this study highlight the notion that myotubes obtained by explanting satellite cells from different muscles are not functionally identical and retain the physiological characteristics of their muscle of origin. Furthermore, our results indicate that sparing of facial and EOMs in patients with Duchenne muscular dystrophy is the result of the higher levels of utrophin expression

Functional diversity of motoneurons in the oculomotor system

Extraocular muscles contain two types of muscle fibers according to their innervation pattern: singly innervated muscle fibers (SIFs), similar to most skeletal muscle fibers, and multiply innervated muscle fibers (MIFs). Morphological studies have revealed that SIF and MIF motoneurons are segregated anatomically and receive different proportions of certain afferents, suggesting that while SIF motoneurons would participate in the whole repertoire of eye movements, MIF motoneurons would contribute only to slow eye movements and fixations. We have tested that proposal by performing single-unit recordings, in alert behaving cats, of electrophysiologically identified MIF and SIF motoneurons in the abducens nucleus. Our results show that both types of motoneuron discharge in relation to eye position and velocity, displaying a tonic–phasic firing pattern for different types of eye movement (saccades, vestibulo-ocular reflex, vergence) and gaze-holding. However, MIF motoneurons presented an overall reduced firing rate compared with SIF motoneurons, and had significantly lower recruitment threshold and also lower eye position and velocity sensitivities. Accordingly, MIF motoneurons could control mainly gaze in the off-direction, when less force is needed, whereas SIF motoneurons would contribute to increase muscle tension progressively toward the on-direction as more force is required. Anatomically, MIF and SIF motoneurons distributed intermingled within the abducens nucleus, with MIF motoneurons being smaller and having a lesser somatic synaptic coverage. Our data demonstrate the functional participation of both MIF and SIF motoneurons in fixations and slow and phasic eye movements, although their discharge properties indicate a functional segregation.Ministerio de Ciencia, Innovación y Universidades – Fondo Europeo de Desarrollo Regional (BFU2015-64515-P)Junta de Andalucía (BIO-297

Extraocular muscle sampled volume in Graves' orbitopathy using 3-T fast spin-echo MRI with iterative decomposition of water and fat sequences

Abstract Background: Current magnetic resonance imaging (MRI) techniques for measuring extraocular muscle (EOM) volume enlargement are not ideally suited for routine follow-up of Graves’ ophthalmopathy (GO) because the difficulty of segmenting the muscles at the tendon insertion complicates and lengthens the study protocol. Purpose: To measure the EOM sampled volume (SV) and assess its correlation with proptosis. Material and Methods: A total of 37 patients with newly diagnosed GO underwent 3-T MRI scanning with iterative decomposition of water and fat (IDEAL) sequences with and without contrast enhancement. In each patient, the three largest contiguous coronal cross-sectional areas (CSA) on the EOM slices were segmented using a polygon selection tool and then summed to compute the EOM-SV. Proptosis was evaluated with the Hertel index (HI). The relationships between the HI value and EOM-SV and between HI and EOM-CSA were compared and assessed with Pearson’s correlation coefficient and the univariate regression coefficient. Inter-observer and intra-observer variability were calculated. Results: HI showed a stronger correlation with EOM-SV (P<0.001; r¼0.712, r2¼0.507) than with EOM-CSA (P<0.001; r¼0.645 and r2¼0.329). The intraclass correlation coefficient indicated that the inter-observer agreement was high (0.998). The standard deviation between repeated measurements was 1.9–5.3%. Conclusion: IDEAL sequences allow for the measurement EOM-SV both on non-contrast and contrast-enhanced scans. EOM-SV predicts proptosis more accurately than does EOM-CSA. The measurement of EOM-SV is practical and reproducible. EOM-SV changes of 3.5–8.3% can be assumed to reflect true volume changes

Genome-wide search for strabismus susceptibility loci.

The purpose of this study was to search for chromosomal susceptibility loci for comitant strabismus. Genomic DNA was isolated from 10mL blood taken from each member of 30 nuclear families in which 2 or more siblings are affected by either esotropia or exotropia. A genome-wide search was performed with amplification by polymerase chain reaction of 400 markers in microsatellite regions with approximately 10 cM resolution. For each locus, non-parametric affected sib-pair analysis and non-parametric linkage analysis for multiple pedigrees (Genehunter software, http://linkage.rockefeller.edu/soft/) were used to calculate multipoint lod scores and non-parametric linkage (NPL) scores, respectively. In sib-pair analysis, lod scores showed basically flat lines with several peaks of 0.25 on all chromosomes. In non-parametric linkage analysis for multiple pedigrees, NPL scores showed one peak as high as 1.34 on chromosomes 1, 2, 4, 7, 10, 15, and 16, while 2 such peaks were found on chromosomes 3, 9, 11, 12, 18, and 20. Non-parametric linkage analysis for multiple pedigrees of 30 families with comitant strabismus suggested a number of chromosomal susceptibility loci. Our ongoing study involving a larger number of families will refine the accuracy of statistical analysis to pinpoint susceptibility loci for comitant strabismus.&#60;/P&#62;</p

Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure.

PurposeWe used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).MethodsSeventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.ResultsAverage mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).ConclusionsAlthough tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP

Visual and control aspects of saccadic eye movements

Physiological, behavioral, and control investigation of rapid saccadic jump eye movement in human

Orbital causes of incomitant strabismus

Strabismus may result from abnormal innervation, structure, or function of the extraocular muscles. Abnormalities of the orbital bones or masses within the orbit may also cause strabismus due to indirect effects on the extraocular muscles. This paper reviews some disorders of the orbit that are associated with strabismus, including craniofacial malformations, orbital masses, trauma, and anomalous orbital structures

Extraocular Muscle Imbalance and Outcomes of Scleral Buckling Surgery for Primary Rhegmatogenous Retinal Detachment

Objective:&nbsp;The objective was to study the muscle imbalance, restrictive motility in unlike gazes and the outcomes of the scleral buckling surgery for rhegmatogenous retinal detachment. Study design:&nbsp;Prospective follow-up study Settings and duration:&nbsp;The study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from Aug 2015 to Jan 2016. Methodology:&nbsp;The patients were checked prior to surgery and two follow up visits were done afterwards. Thorough history was taken along with full orthoptic assessment and ocular motility in all four main gazes including elevation, depression, adduction and abduction. Vision, type and position of explants, site of detachment, and risk factors of detachment were also observed. Results:&nbsp;A total of 48 eyes of 46 patients were taken. Mean age of the study participants was 37.16±20.37 years. Horizontal, vertical and combined deviations were observed in study population. Exo deviation was most common deviation among patients. Most reported risk factors of retinal detachment included trauma, pseudophakia, aphakia and myopia. Motility limitations of all four gazes was observed and it was found out that after buckling the squint and restriction is been increased up till two months. Conclusion:&nbsp;Ocular restriction among the patients was observed over a period of 2 months and it depicted that encircling with sclera buckling elicited an increase in restrictive ocular motility from pre-operative to 1 week and 2 months after surgery

Vascular Endothelial Growth Factor (VEGF) Prevents the Downregulation of the Cholinergic Phenotype in Axotomized Motoneurons of the Adult Rat

Vascular endothelial growth factor (VEGF) was initially characterized by its activity on the vascular system. However, there is growing evidence indicating that VEGF also acts as a neuroprotective factor, and that its administration to neurons suffering from trauma or disease is able to rescue them from cell death. We questioned whether VEGF could also maintain damaged neurons in a neurotransmissive mode by evaluating the synthesis of their neurotransmitter, and whether its action would be direct or through its well-known angiogenic activity. Adult rat extraocular motoneurons were chosen as the experimental model. Lesion was performed by monocular enucleation and immediately a gelatine sponge soaked in VEGF was implanted intraorbitally. After 7 days, abducens, trochlear, and oculomotor nuclei were examined by immunohistochemistry against choline acetyltransferase (ChAT), the biosynthetic enzyme of the motoneuronal neurotransmitter acetylcholine. Lesioned motoneurons exhibited a noticeable ChAT downregulation which was prevented by VEGF administration. To explore whether this action was mediated via an increase in blood vessels or in their permeability, we performed immunohistochemistry against laminin, glucose transporter-1 and the plasmatic protein albumin. The quantification of the immunolabeling intensity against these three proteins showed no significant differences between VEGF-treated, axotomized and control animals. Therefore, the present data indicate that VEGF is able to sustain the cholinergic phenotype in damaged motoneurons, which is a first step for adequate neuromuscular neurotransmission, and that this action seems to be mediated directly on neurons since no sign of angiogenic activity was evident. These data reinforces the therapeutical potential of VEGF in motoneuronal diseases.España, MINECO and FEDER BFU2015-64515-PJunta de Andalucía and FEDER : P10-CVI605

Orbital pseudotumour masquerading as Wegener’s granulomatosis

A twenty-two year old female patient presented with new onset bilateral hard orbital masses and progressively worse tear lake problems. Computed tomography of the orbits revealed poorly differentiated bilateral orbital masses. Laboratory investigation revealed ANCA positivity. Routine biochemical investigations were all within normal limits. CXR was also normal. Biopsy of the orbital masses revealed non-specific histological findings. An initial diagnosis of Granulomatosis with Polyangitis (GPA) was postulated. Oral steroids were given followed by a rapid response to steroid therapy. The working diagnosis of GPA was abandoned and a diagnosis of idiopathic orbital inflammation (IOI), or orbital pseudotumour was made owing to the benign, non-infective, inflammatory pathology with no evident systemic or local cause. Tailoring off of steroids resulted in repeated flare ups, resulting in the initiation of methotrexate therapy. The patient is in remission and is currently on combined steroid and methotrexate treatment. IOI is a diagnosis of exclusion and a rapid response to steroids serves as a diagnostic aid but is not in itself diagnostic.peer-reviewe