Extraocular muscle stem cells exhibit distinct cellular properties associated with non-muscle molecular signatures.

Skeletal muscle stem cells (MuSCs) are recognised as functionally heterogeneous. Cranial MuSCs are reported to have greater proliferative and regenerative capacity when compared with those in the limb. A comprehensive understanding of the mechanisms underlying this functional heterogeneity is lacking. Here, we have used clonal analysis, live imaging and single cell transcriptomic analysis to identify crucial features that distinguish extraocular muscle (EOM) from limb muscle stem cell populations. A MyogeninntdTom reporter showed that the increased proliferation capacity of EOM MuSCs correlates with deferred differentiation and lower expression of the myogenic commitment gene Myod. Unexpectedly, EOM MuSCs activated in vitro expressed a large array of extracellular matrix components typical of mesenchymal non-muscle cells. Computational analysis underscored a distinct co-regulatory module, which is absent in limb MuSCs, as driver of these features. The EOM transcription factor network, with Foxc1 as key player, appears to be hardwired to EOM identity as it persists during growth, disease and in vitro after several passages. Our findings shed light on how high-performing MuSCs regulate myogenic commitment by remodelling their local environment and adopting properties not generally associated with myogenic cells.

MYH13, a superfast myosin expressed in extraocular, laryngeal and syringeal muscles.

MYH13 is a unique type of sarcomeric myosin heavy chain (MYH) first detected in mammalian extraocular (EO) muscles and later also in vocal muscles, including laryngeal muscles of some mammals and syringeal muscles of songbirds. All these muscles are specialized in generating very fast contractions while producing relatively low force, a design appropriate for muscles acting against a much lower load than most skeletal muscles inserting into the skeleton. The definition of the physiological properties of muscle fibres containing MYH13 has been complicated by the mixed fibre type composition of EO muscles and the coexistence of different MYH types within the same fibre. A major advance in this area came from studies on isolated recombinant myosin motors and the demonstration that the affinity of actin-bound human MYH13 for ADP is much weaker than those of fast-type MYH1 (type 2X) and MYH2 (type 2A). This property is consistent with a very fast detachment of myosin from actin, a major determinant of shortening velocity. The MYH13 gene arose early during vertebrate evolution but was characterized only in mammals and birds and appears to have been lost in some teleost fish. The MYH13 gene is located at the 3' end of the mammalian fast/developmental gene cluster and in a similar position to the orthologous cluster in syntenic regions of the songbird genome. MYH13 gene regulation is controlled by a super-enhancer in the mammalian locus and deletion of the neighbouring fast MYH1 and MYH4 genes leads to abnormal MYH13 expression in mouse leg muscles.

MRI evaluation of cranial nerve abnormalities and extraocular muscle fibrosis in duane retraction syndrome and congenital extraocular muscle fibrosis.

PURPOSE: To investigate the alterations in extraocular muscles (EOMs) by magnetic resonance imaging (MRI) among patients diagnosed with Duane retraction yndrome (DRS) and congenital fibrosis of the extraocular muscles (CFEOM), who present with various cranial nerve anomalies in an attempt to enhance the clinical diagnostic process. METHODS: A case-control study was conducted to evaluate 27 patients with DRS and 14 patients with CFEOM. All patients underwent MRI scans of the brainstem and orbital examination. Neurodevelopmental assessments were conducted through MRI, and maximum cross-sectional area and volumes of EOMs were obtained. Three types of models were constructed using machine learning decision tree algorithms based on EOMs to predict disease diagnosis, cranial nerve abnormalities, and clinical subtypes. RESULTS: Patients with bilateral CN VI abnormalities had smaller volumes of LR, MR, and IR muscles compared to those with unilateral involvement (P < 0.05). Similarly, patients with CFEOM and unilateral third cranial nerve abnormalities had a smaller maximum cross-section of the affected eye's SR compared to the contralateral eye (P < 0.05). In patients with both CN III and CN VI abnormalities, the volume of SR was smaller than in patients with CN III abnormalities alone (P < 0.05). The prediction model using EOMs volume showed a diagnostic precision of 82.5% for clinical cases and 60.1% for predicting cranial nerve abnormalities. Nonetheless, the precision for identifying clinical subtypes was relatively modest, at only 41.7%. CONCLUSION: The distinctive volumetric alterations in EOMs among individuals exhibiting distinct cranial nerve anomalies associated with DRS or CFEOM provide valuable diagnostic insights into to Congenital Cranial Neurodevelopmental Disorders (CCDDs). MRI analysis of EOMs should thus be regarded as a crucial diagnostic modality.

Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.

Development of the extraocular muscles during the fetal period.

PURPOSE: The aim of this study was to investigate the morphometric development of the extraocular muscles in the fetal period and to create a modified Tillaux spiral. METHODS: We dissected 157 fetal eyes (82 right eyes, 75 left eyes) obtained from 79 fetuses (46 boys, 33 girls) between 13 and 40 weeks of gestation. The tendon widths of the extraocular muscles and the distances of the tendon attachment sites to the limbus were measured. Tillaux's modified spiral was created. RESULTS: In addition to the rectus muscles, we added tendon widths and tendon-limbus distances of the upper (SO) and lower (IO) obliques to the modified Tillaux spiral. When tendon widths were compared between genders, no statistically significant difference was observed. When tendon widths were compared between the sides, it was determined that SO was more in the left eye, whereas other extraocular muscles were more in the right eye. There was no statistically significant difference between genders when the distances of tendon attachment sites to the limbus were compared. There was no statistically significant difference in SO and IO values between the sides. There was a statistically significant difference in the rectus muscles and this difference was found to be higher in the right eye. CONCLUSION: We think that the findings obtained will contribute to disciplines such as fetopathology, obstetrics, ophthalmology and plastic surgery and to future studies on this subject.

Echographic characterization of extraocular muscles in pediatric patients with thyroid dysfunction.

PURPOSE: To characterize the size of extraocular muscles (EOMs) in a pediatric population with thyroid dysfunction using orbital echography. METHODS: Patients under age 18 with thyroid dysfunction who presented to an academic ophthalmology department from 2009 to 2020 and received orbital echography were included in this IRB-approved retrospective study. Data collected included age, clinical activity score (CAS), thyroid stimulating immunoglobulin (TSI), and extraocular recti muscle thickness on echography. Patients were organized into three age cohorts, after which statistical analysis compared recti measurements to previously reported normal ranges. RESULTS: Twenty patients with thyroid dysfunction were included. When comparing average recti muscle thicknesses of study patients to those of previously published normal children in similar age ranges, the levator-superior rectus complex was significantly increased in all age groups of children with thyroid dysfunction (p-values = <.004), and the levator-superior rectus complex was most frequently enlarged compared to published normal values (78% of eyes). CAS was not correlated with EOM size in the youngest group (5-10 years old, p-values >.315) but was significantly correlated in older groups (11-17 years old, p-values <.027). TSI was not correlated with EOM size in any group (p-values >.206). CONCLUSIONS: Echographic reference ranges for EOMs in children with thyroid dysfunction were established. There are increased rates of levator-superior rectus complex enlargement in children with TED compared to adults with TED, and EOM size is correlated with CAS in children older than 10 years. Though limited, these findings may serve as an additional tool for ophthalmologists to ascertain disease activity in pediatric patients with thyroid dysfunction.

TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscle organization in mouse.

Heterozygous loss of function mutations in TWIST1 cause Saethre-Chotzen syndrome, which is characterized by craniosynostosis, facial asymmetry, ptosis, strabismus, and distinctive ear appearance. Individuals with syndromic craniosynostosis have high rates of strabismus and ptosis, but the underlying pathology is unknown. Some individuals with syndromic craniosynostosis have been noted to have absence of individual extraocular muscles or abnormal insertions of the extraocular muscles on the globe. Using conditional knock-out alleles for Twist1 in cranial mesenchyme, we test the hypothesis that Twist1 is required for extraocular muscle organization and position, attachment to the globe, and/or innervation by the cranial nerves. We examined the extraocular muscles in conditional Twist1 knock-out animals using Twist2-cre and Pdgfrb-cre drivers. Both are expressed in cranial mesoderm and neural crest. Conditional inactivation of Twist1 using these drivers leads to disorganized extraocular muscles that cannot be reliably identified as specific muscles. Tendons do not form normally at the insertion and origin of these dysplastic muscles. Knock-out of Twist1 expression in tendon precursors, using scleraxis-cre, however, does not alter EOM organization. Furthermore, developing motor neurons, which do not express Twist1, display abnormal axonal trajectories in the orbit in the presence of dysplastic extraocular muscles. Strabismus in individuals with TWIST1 mutations may therefore be caused by abnormalities in extraocular muscle development and secondary abnormalities in innervation and tendon formation.

Comitant strabismus etiology: extraocular muscle integrity and central nervous system involvement-a narrative review.

Strabismus is not a condition in itself but the consequence of an underlying problem. Eye misalignment can be caused by disease, injury, and/or abnormalities in any of the structures and processes involved in visual perception and oculomotor control, from the extraocular muscles and their innervations to the oculomotor and visual processing areas in the brain. A small percentage of all strabismus cases are the consequence of well-described genetic syndromes, acquired insult, or disease affecting the extraocular muscles (EOMs) or their innervations. We will refer to them as strabismus of peripheral origin since their etiology lies in the peripheral nervous system. However, in most strabismus cases, that is comitant, non-restrictive, non-paralytic strabismus, the EOMs and their innervations function properly. These cases are not related to specific syndromes and their precise causes remain poorly understood. They are generally believed to be caused by deficits in the central neural pathways involved in visual perception and oculomotor control. Therefore, we will refer to them as central strabismus. The goal of this narrative review is to discuss the possible causes behind this particular type of eye misalignment and to raise awareness among eyecare professionals about the important role the central nervous system plays in strabismus etiology, and the subsequent implications regarding its treatment. A non-systematic search was conducted using PubMed, Medline, Cochrane, and Google Scholar databases with the keywords "origins," "causes," and "etiology" combined with "strabismus." A snowball approach was also used to find relevant references. In the following article, we will first describe EOM integrity in central strabismus; next, we will address numerous reasons that support the idea of central nervous system (CNS) involvement in the origin of the deviation, followed by listing several possible central causes of the ocular misalignment. Finally, we will discuss the implications CNS etiology has on strabismus treatment.

Clinical significance of CTGF and Cry61 protein in extraocular muscles of strabismic patients.

PURPOSE: To investigate the relationship between clinical features and protein amounts of Cysteine-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2), which are vital components and regulators of the extracellular matrix in resected muscles from strabismus surgery. METHODS: Strabismus patients who were diagnosed with horizontal concomitant strabismus or inferior oblique overaction (IOOA) and required extraocular muscles (EOMs) resection to correct eye position were included in this study. The protein amounts were measured by enzyme-linked immunosorbent assay (ELISA) in resected EOMs. Multivariable linear regression was used to investigate the associations, adjusting for gender, age (continuous), amblyopia, and disease duration. RESULTS: A total of 141 muscles (including 38 lateral, 81 medial rectus, and 22 inferior oblique muscles) from 128 patients were collected in this study. The amount of Cry61 and CTGF per millimeter was significantly negatively associated with deviation angle in intermittent exotropia patients (Cry61: ß, - 1.44; 95%CI, - 2.79 to - 0.10, p = 0.035; CTGF: ß, - 3.14; 95%CI, - 5.06 to - 1.22, p = 0.002). The same relationship was also detected in the partially accommodative and non-accommodative esotropia patients, although it was not statistically significant (Cry61: ß, - 2.40; 95%CI, - 5.05 to 0.24; p = 0.073; CTGF: ß, - 3.47; 95%CI, - 9.18 to 2.87; p = 0.269). The amount of Cry61 and CTGF per millimeter showed significant associations with the degree of IOOA (p < 0.05). CONCLUSIONS: Taken together, our results demonstrated a significant relationship between deviation angle and protein amount of Cry61 and CTGF and implied that Cry61 and CTGF may play important roles in modulation of EOM contractility, which provide new insights into strabismus pathogenesis.

Normative orbital measurements in an Australian cohort on computed tomography.

PURPOSE: To determine the normal diameters of the extraocular muscles (EOMs) and optic nerve sheath complex (ONSD) and correlate with patient demographics in an Australian cohort. METHODS: Consecutive patients who underwent contrast enhanced computed tomography (CT) orbits between December 2017 and March 2021 were included. Patients with bilateral disease, previous orbital surgery, or poor scan quality were excluded. Normal orbit was used in patients with unilateral orbital disease. RESULTS: Two hundred one orbits from 201 patients were included. Normal measurements (mean ± SD) were as follows: medial rectus (MR) 4.22 ± 0.56 mm; inferior rectus (IR) 4.20 ± 0.70 mm; lateral rectus (LR) 3.40 ± 0.56 mm; superior muscle group (SMG) 4.13 ± 0.72 mm; superior oblique (SO) 2.60 ± 0.43 mm; inferior oblique (IO) on quasi-sagittal plane 2.19 ± 0.42 mm, and the ONSD 5.62 ± 0.82 mm. The mean diameters of the LR, SMG, IR, SO, and ONSD were significantly larger in male than female patients (p < .05). Statistically significant correlation was found between age and the diameters of the LR (r = 0.29, p < .01), SMG (r = 0.22, p < .01), IO on a coronal plane (r = -0.18, p < .01), and ONSD (r = 0.16, p = .02). CONCLUSION: This normative data may be used to diagnose pathological enlargement of the optic nerve and extraocular muscles, including involvement of the oblique muscles.

A new treatment modality for the enlarged extraocular muscles.

PURPOSE: evaluation of the role of combined injection of triamcinolone acetonide with 5 Fluorouracil in treatment of the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation. METHODS: injection of 0.1 ml of triamcinolone acetonide 40 mg/ml and 0.1 ml of 5 Fluorouracil 50 mg/ml in the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation in 6 patients, after the confirmation of the histopathological diagnosis of these patients by revising their medical records. RESULTS: There was a significant improvement in the visual acuity, in addition to a significant improvement also in the clinical and the radiological features in the patients who were consented for the trial of the new injection protocol. However, there was failure of clinical and radiological improvement in one case presented with sever fibrosis. There was a significant absence of the side effects in all patients except for one patient that reported discomfort near the inner canthus. CONCLUSION: The new protocol of the treatment is a promising modality that can be used in the chronic non-infectious inflammation without extensive fibrosis.

Role of muscle biopsy in diagnosis of extraocular muscles enlargement.

PURPOSE: To study the role of muscle biopsy in patients with enlarged extraocular muscles. METHODS: A retrospective review of 31 patients who underwent biopsy for extraocular muscle enlargement. Characteristics, including signs, symptoms, imaging findings, and histopathological assessment were examined. RESULTS: Chronic inflammatory disorders represented the most common cause of the muscle enlargement followed by malignancy/metastasis. Multiple muscle involvement was more consistent with benign diseases, whereas single muscle involvement was more consistent with malignant causes. Positive predictive value of muscle biopsy was 0.52 for determining a specific cause of the muscle enlargement. CONCLUSIONS: Muscle biopsy is the standard for diagnosis in patients with extraocular muscle enlargement. This diagnostic test should be performed in every case of non-resolving muscle enlargement, with a specific diagnosis being made in over half of cases.

Proprioceptive contribution to oculomotor control in humans.

Stretch receptors in the extraocular muscles (EOMs) inform the central nervous system about the rotation of one's own eyes in the orbits. Whereas fine control of the skeletal muscles hinges critically on proprioceptive feedback, the role of proprioception in oculomotor control remains unclear. Human behavioural studies provide evidence for EOM proprioception in oculomotor control, however, behavioural and electrophysiological studies in the macaque do not. Unlike macaques, humans possess numerous muscle spindles in their EOMs. To find out whether the human oculomotor nuclei respond to proprioceptive feedback we used functional magnetic resonance imaging (fMRI). With their eyes closed, participants placed their right index finger on the eyelid at the outer corner of the right eye. When prompted by a sound, they pushed the eyeball gently and briefly towards the nose. Control conditions separated out motor and tactile task components. The stretch of the right lateral rectus muscle was associated with activation of the left oculomotor nucleus and subthreshold activation of the left abducens nucleus. Because these nuclei control the horizontal movements of the left eye, we hypothesized that proprioceptive stimulation of the right EOM triggered left eye movement. To test this, we followed up with an eye-tracking experiment in complete darkness using the same behavioural task as in the fMRI study. The left eye moved actively in the direction of the passive displacement of the right eye, albeit with a smaller amplitude. Eye tracking corroborated neuroimaging findings to suggest a proprioceptive contribution to ocular alignment.

Characteristics of Diabetic and Nondiabetic Patients With Thyroid Eye Disease in the United States: A Claims-Based Analysis.

OBJECTIVE: Thyroid eye disease (TED) is a debilitating autoimmune disease characterized by ocular and periorbital tissue inflammation, proptosis, and visual impairment. The known risk factors for TED include radioactive iodine therapy, female sex, and smoking. The risk factors for severe TED include hyperthyroidism, male sex, smoking, and diabetes; however, little is known about how diabetes mellitus (DM) influences TED. This claims-based analysis examined TED characteristics in patients with and without diabetes. METHODS: Symphony database (2010-2015 U.S. claims) was mined for patients with ≥1 Graves' disease diagnosis code and ≥1 TED-associated eye code, including proptosis, strabismus, diplopia, lid retraction, exposure keratoconjunctivitis, and optic neuropathy (ON). DM status was determined based on type 1 or type 2 diabetes coding. Sight-threatening TED was defined as ≥1 ON or exposure keratoconjunctivitis code. RESULTS: A total of 51 220 patients were identified. Of them, 2618 (5.1%) and 12 846 (25.1%) had type 1 and type 2 DM, respectively. Patients with and without DM had similar characteristics, but patients with DM were more often men (type 1: 30.3%, type 2: 28.7% vs no DM: 20.5%; both P < .001) and older at the first TED code. In patients with DM, strabismus (25.4%, 22.6% vs 19.9%) and diplopia (38.6%, 37.9% vs 29.9%) occurred more often but proptosis occurred less often (42.3%, 46.3% vs 58.5%; all P < .001). Sight-threatening TED occurred more often in patients with DM because of higher ON rates. CONCLUSION: Patients with TED and DM may have more extraocular muscle involvement. Furthermore, the higher prevalence of severe TED stemmed from higher ON rates, possibly associated with diabetes-related vasculopathies. These hypothesis-generating data warrant further exploration.

Age-related difference in extraocular muscles and its relation to clinical manifestations in an ethnically homogenous group of patients with Graves' orbitopathy.

PURPOSE: To evaluate the age-related difference in EOMs and its relation to clinical manifestations by computed tomography (CT) measurement of EOMs. METHODS: The medical records and CT image review of 40 patients (80 orbits) with moderate-to-severe Graves' orbitopathy were performed. The patients were divided into two age groups, group 1 (≤ 40 years) and group 2 (> 40 years). CT scans of 30 gender- and age-matched normal controls were also obtained. The maximal cross-sectional area (MCA) and its position (pMCA) of each EOM were measured. RESULTS: Group 1 presented with more severe proptosis (p < 0.001), while group 2 had a higher risk of diplopia (p < 0.001). Motility restriction in supraduction was more likely to occur in Group 2 (p = 0.027) with even higher severity (p = 0.047). The pMCA was higher in the inferior (p = 0.001), medial (p = 0.021), and lateral rectus (p = 0.013) in group 1. Proptosis was positively correlated to pMCA while diplopia was correlated to MCA in both groups. Significant correlation was noted between restrictions levels and MCA (superior, r = 0.467, p < 0.001; inferior, r = 0.358, p = 0.007; medial, r = 0.314, p = 0.018; lateral, r = 0.308, p = 0.021) or pMCA (inferior, r = - 0.534, p < 0.001) only in group 2. CONCLUSIONS: The muscle enlargement patterns are significantly different between younger and older patients. Older patients tended to have enlarged muscle bellies more posterior in the orbit, which is responsible for more diplopia and motility restriction. Proptosis is more likely to be affected by the most enlarged position than muscle size. So younger patients tended to develop more proptosis and be less bothered by motility restriction even with enlarged muscles.

Ocular hypertension in patients with active thyroid-associated orbitopathy: a predictor of disease severity, particularly of extraocular muscle enlargement.

The purpose was to ascertain if any relation exists between the elevated intraocular pressure (IOP) in patients with thyroid-associated orbitopathy (TAO) in active stage and the severity of extraocular muscle involvement and the extent of exophthalmos. METHODS: A total of 96 eyes and orbits of 48 adult patients with active TAO were investigated. All patients underwent magnetic resonance imaging of the orbit and measurement of all extraocular recti muscles (EOM). The obtained data was divided into two groups according to the IOP value: normal IOP ≤ 21 mmHg; n = 47 and elevated IOP with IOP > 21 mmHg; n = 49, and analyszed. RESULTS: A significant difference was found in the short diameter of medial rectus and inferior rectus muscles and in the sum of short parameters of all EOM. All these parameters were significantly higher in the elevated IOP group. Motility restriction in at least one gaze direction was also significantly more frequent (p < 0.0001) in the elevated IOP group. A positive moderate correlation was found between IOP and the sum of short parameters of EOM (r = 0.496). No correlation was found between the IOP and exophthalmos values (r = 0.267). During the follow-up, the frequency of strabismus surgery and orbital decompression was significantly higher in the elevated IOP group (p = 0.003; p = 0.002). CONCLUSION: Elevated IOP in the active TAO stage particularly correlates with extraocular muscle involvement. These patients are also more likely to require orbital decompression and strabismus surgery.

Correlation between extent of lacrimal gland prolapse and clinical features of thyroid-associated ophthalmopathy: a retrospective observational study.

BACKGROUND: Studies on the factors related to lacrimal gland prolapse (LGP) in patients with thyroid-associated ophthalmopathy (TAO) are limited. This study aimed to assess the factors associated with LGP on magnetic resonance imaging (MRI) and its relation to TAO activity . METHODS: Thirty-six patients (72 orbits) with inactive TAO (43 orbits, Clinical Activity Score [CAS] < 3) or active TAO (29 orbits, CAS ≥3) were investigated retrospectively. All patients underwent ophthalmic evaluation and orbital magnetic resonance imaging. The severity of LGP and proptosis and the extraocular muscle (EOM) volume were measured. LGP and related factors were assessed by correlational and linear regression analyses. The value of LGP for discriminating the activity of TAO was evaluated by receiver-operating characteristic curve analysis. RESULTS: The mean LGP was significantly higher in the active TAO group than in the inactive TAO group (P < 0.001). There were significant positive correlations between LGP severity and the CAS (r = 0.51, P < 0.001), proptosis (r = 0.72, P < 0.001), and EOM volume (superior rectus [r = 0.49, P < 0.001], inferior rectus [r = 0.47, P < 0.001], lateral rectus [r = 0.59, P < 0.001], medial rectus [r = 0.62, P < 0.001], superior oblique [r = 0.48, P < 0.001], and all EOMs [r = 0.59, P < 0.001]). Receiver-operating characteristic curve analysis revealed an LGP of 13.65 mm (area under the curve, 0.824; sensitivity, 79.3%; specificity, 81.4%) to be the cut-off value that differentiated active and inactive TAO. CONCLUSIONS: LGP measurements obtained from orbital magnetic resonance images were positively correlated with CAS, proptosis and EOM volume. The extent of LGP appears to be a good indicator of disease activity in patients with TAO.

Histopathological changes in extraocular muscles of rabbits following injection of bupivacaine 5mg/Ml versus 7.5mg/Ml.

PURPOSE: To compare the histopathological effects of injecting two concentrations of Bupivacaine (5 mg/ml and 7.5 mg/ml) in the superior rectus muscle of rabbits, and to compare these to conventional extraocular muscle surgery in previous studies. METHODS: Eighteen albino rabbits' eyes were used. The superior rectus muscles were injected with Bupivacaine 5 mg/ml (Group B5, 10 eyes) or 7.5 mg/ml (Group B7, 8 eyes). The rabbits were sacrificed and eyes enucleated 6 weeks later for histopathological evaluation. Results were compared to the average of those obtained, by three previous studies, after conventional superior rectus resection in rabbits. RESULTS: Foreign body reaction was absent in all specimens. Conjunctival and scleral inflammation, perimuscular adhesions, intramuscular fibrosis, conjunctival and scleral oedema and muscle atrophy were higher in group B7, while conjunctival hyperaemia and muscle hypertrophy were higher in group B5 (p > 0.05). On comparison to conventional surgery, conjunctival inflammation and hyperaemia, foreign body reaction, and adhesions were less after bupivacaine injection (p > 0.05 for all except for intensity of conjunctival inflammation in B5 versus conventional surgery). Scleral inflammation was more frequent after bupivacaine injection (p < 0.05). Muscle fibrosis was more frequent in group B7 and conventional surgery than in group B5 (p > 0.05). CONCLUSIONS: Both Bupivacaine concentrations effectively produced the desired muscle hypertrophy and fibrosis, so the lower concentration may be used for muscle strengthening to correct strabismus. Bupivacaine injection, although produced no foreign body reaction, did not significantly lower the development of undesired postoperative adhesions and caused more scleral inflammation.

Preserved eye movements in adults with spinal muscular atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) most prominently affects proximal limb and bulbar muscles. Despite older case descriptions, ocular motor neuron palsies or other oculomotor abnormalities are not considered part of the phenotype. METHODS: We investigated oculomotor function by testing saccadic eye movements of 15 patients with SMA. Their performance was compared with that of age-matched healthy controls. Horizontal rightward and leftward saccades were recorded by means of video-oculography, whereas subjects looked at light-emitting diode targets placed at ±5°, ±10°, and ±15° eccentricities. RESULTS: No differences in saccade amplitude gains, peak velocities, peak velocity-to-amplitude ratios, or durations were observed between controls and patients. More specifically, for 5° target eccentricities, patients had a mean saccadic peak velocity of 153°/s, whereas for 10° and 15° these values were 268°/s and 298°/s, respectively. The corresponding mean peak velocities of the control group were 151°/s, 264°/s, and 291°/s. DISCUSSION: Our results indicate that patients with SMA perform fast and accurate horizontal saccades without evidence of extraocular muscle weakness. These quantitative oculomotor data corroborate clinical experience that neuro-ophthalmic symptoms in SMA are not common and, if present, should prompt suspicion for an alternative neuromuscular disorder.

MRI evidence of extraocular muscle atrophy and fatty replacement in myasthenia gravis.

PURPOSE: The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. METHODS: Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. RESULTS: Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. CONCLUSION: EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement.