Changes In Extraocular Muscles Research Articles

Subclinical Ocular Motility Dysfunction and Extraocular Muscle Changes in Inactive Graves' Orbitopathy.

This study aimed to investigate the presence of structural and functional changes in extraocular muscles (EMs) among patients with inactive Graves' orbitopathy (GO) classified according to the Clinical Activity Score (CAS). Sixty-seven patients with Graves' disease (GD) and inactive GO were included. The data collected included clinical parameters, thyroid function, autoantibody levels, EOM morphology via orbital ultrasound (US), and ocular motility. Patients were stratified into Red Filter Test (RFT)-positive or RFT-negative groups based on the presence or absence of latent diplopia during the RFT examination. Thirty-three patients (49.25%) exhibited latent diplopia on the RFT, despite not reporting double vision during standard ocular motility tests. Significant differences were observed between the two groups in terms of age, disease duration, intraocular pressure (IOP) elevation in up-gaze, and medial rectus muscle thickness (p < 0.05). No significant differences were found in thyroid status, TRAb and ATA levels, CASs, exophthalmos, or lateral rectus thickness between the two groups. This study revealed that in inactive GO, subclinical EM dysfunction and morphological changes may be present, which might not be apparent through routine ocular examinations. The RFT is effective in detecting latent diplopia, highlighting its utility in identifying subtle ocular motility issues and subclinical muscle involvement. Comprehensive evaluations combining functional tests like the RFT and imaging are essential for early detection of GO-related abnormalities, enabling tailored and prompt management and improving patient outcomes.

Clinical efficacy of modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia

Objective: To investigate the clinical efficacy of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia. Methods: A retrospective case series study was conducted. Clinical data were collected from patients who underwent the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia at Eye Hospital of Shandong First Medical University from February 2017 to February 2022. During the procedure, the superior rectus and lateral rectus muscles were fully separated. A longitudinal blunt incision was made in the central muscle belly extending posteriorly to 12-14 mm from the muscle insertion. The temporal half of the superior rectus muscle and the upper half of the lateral rectus muscle belly were transposed and secured to the contralateral muscle insertion. Simultaneously, medial rectus muscle recession was performed. Follow-up visits were conducted at 1 week, 1 month, 3 months, and 6 months postoperatively. Patients' ocular alignment, eye movements, improvement in compensatory head posture, objective degrees of strabismus using synoptophore, changes in extraocular muscles and globe position on orbital CT scan were recorded. Surgical complications were also documented. Results: Five patients (8 eyes) were included in this study, including 4 females (7 eyes) and 1 male (1 eye), with an average age of (63±11) years and an average axial length of (34.58±2.25) mm. The medial rectus muscle recession during surgery was (7.6±2.3) mm. Preoperatively, all patients had esotropia with a horizontal range of+15°to+45° and a vertical range of+15°to+45°. Significant limitations in lateral and upward gaze were observed, with a degree of restriction ranging from-3 (-4 to-1). Three patients with bilateral involvement and one patient with unilateral involvement exhibited significant compensatory head postures. One patient with unilateral involvement had no compensatory head posture. Preoperative orbital CT scans indicated nasal displacement of the superior rectus muscle and inferior displacement of the lateral rectus muscle, with the eyeball herniating from the muscle cone. At the 6-month follow-up, all patients achieved nearly orthophoric alignment. Objective degrees of horizontal strabismus ranged from-4°to+7°, and vertical strabismus ranged from 0°to +6°, as determined by synoptophore examination. Eye movements significantly improved, with a degree of restriction of-1 (-2 to-1) for lateral gaze and-2 (-3 to-1) for upward gaze. Compensatory head postures disappeared, and orbital CT scans indicated the eyeball was located within the muscle cone. There were no severe complications such as anterior segment ischemia, muscle adhesions, disease recurrence, secondary glaucoma, or globe penetration. Conclusion: The preliminary clinical outcomes of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia are promising.

Identification and characterization of differentially expressed circular RNAs in extraocular muscle of oculomotor nerve palsy

BackgroundOculomotor nerve palsy (ONP) is a neuroparalytic disorder resulting in dysfunction of innervating extraocular muscles (EOMs), of which the pathological characteristics remain underexplored.MethodsIn this study, medial rectus muscle tissue samples from four ONP patients and four constant exotropia (CXT) patients were collected for RNA sequencing. Differentially expressed circular RNAs (circRNAs) were identified and included in functional enrichment analysis, followed by interaction analysis with microRNAs and mRNAs as well as RNA binding proteins. Furthermore, RT-qPCR was used to validate the expression level of the differentially expressed circRNAs.ResultsA total of 84 differentially expressed circRNAs were identified from 10,504 predicted circRNAs. Functional enrichment analysis indicated that the differentially expressed circRNAs significantly correlated with skeletal muscle contraction. In addition, interaction analyses showed that up-regulated circRNA_03628 was significantly interacted with RNA binding protein AGO2 and EIF4A3 as well as microRNA hsa-miR-188-5p and hsa-miR-4529-5p. The up-regulation of circRNA_03628 was validated by RT-qPCR, followed by further elaboration of the expression, location and clinical significance of circRNA_03628 in EOMs of ONP.ConclusionsOur study may shed light on the role of differentially expressed circRNAs, especially circRNA_03628, in the pathological changes of EOMs in ONP.

Effects of various extraocular muscle enlargement patterns on muscle diameter index in graves ophthalmopathy patients: a retrospective cohort study

Graves ophthalmopathy (GO) patients often undergo retrobulbar injection of glucocorticoids (GCs) as a common therapeutic approach. This study aimed to explore the impact of various patterns of extraocular muscle (EOM) enlargement on EOM changes following retrobulbar GCs injection in patients with GO. A retrospective analysis was conducted on GO patients who underwent retrobulbar GCs injections. Data pertaining to EOM diameter (EMD) and muscle diameter index (MDI) were collected from orbital computed tomography (CT) scans. The MDI change (ΔMDI) was calculated by comparing pre- and post-injection MDI values. The relationship between each pre EMD/MDI and ΔMDI was assessed using univariate and multivariate logistic regression analysis. A total of 68 patients with GO were included in this study, accounting for 118 eyes. After retrobulbar injections of GCs, 84 eyes showed a decrease in the MDI, while 34 eyes exhibited an increase in MDI. A threshold effect was observed in the relationship between medial pre EMD/MDI and ΔMDI. When the medial pre EMD/MDI was less than 0.28, a higher medial pre EMD/MDI was associated with a smaller ΔMDI (β = − 25.21, p = 0.0175). However, when the medial pre EMD/MDI was greater than 0.28, no significant association was found between pre EMD/MDI and ΔMDI. There was a negative correlation between medial + lateral pre EMD/MDI and ΔMDI (β = − 11.76, p < 0.0189). A higher medial + lateral pre EMD/MDI was associated with a greater decrease in MDI. Additionally, there was a positive correlation between superior rectus muscle-levator complex (SRLC) pre EMD/MDI and ΔMDI (β = 11.92, p = 0.040). The higher the value of SRLC pre EMD/MDI, the greater the ΔMDI. There was an association between pre EMD/MDI and changes in EOMs after retrobulbar injection of GCs in GO patients. In patients with predominantly enlarged medial rectus muscles and severe degrees of enlargement, retrobulbar injection of GCs should be assessed for its benefit; a combination of medial and lateral rectus muscle enlargement is beneficial for the shrinkage of EOMs following retrobulbar injections; the involvement of the SRLC rectus muscle may be a disadvantageous pattern of shrinkage of EOMs following retrobulbar injections.Trial registration This study is retrospectively registered. We have registered this study with the Chinese Clinical Trials Registry (www.chictr.org.cn, registration number: ChiCTR2200063429).

Reduction in Extraocular Muscle Cross-sectional Area and Correlation With Extraocular Motility and Diplopia Following Teprotumumab for Thyroid Eye Disease.

To quantify changes in extraocular muscle (EOM) cross-sectional areas (CSA) on orbital imaging in patients with thyroid eye disease before and after teprotumumab treatment, and assess for correlation with clinical outcomes. This retrospective study included thyroid eye disease patients treated with teprotumumab who had pre- and post-treatment CT imaging. Reformatted oblique coronal images were created for each orbit in a plane perpendicular to the optic nerve. EOM CSA measurements were performed by 2 radiographic reviewers and averaged. Primary outcomes included change in ratio of total EOM to orbit CSA, and of each individual muscle group to orbit CSA, before and after treatment. Secondary outcomes included subanalysis based on age (≥40, <40 years) and Clinical Activity Score (CAS) (≥4, <4), and comparison with clinical outcomes including CAS, Hertel exophthalmometry, Gorman diplopia score, and extraocular motility. Forty-eight orbits of 24 patients (16 female, mean age 57.9 years) were included. There was a significant reduction in the total EOM to orbit CSA ratio ( p < 0.01) and for each individual rectus muscle to orbit CSA ratio ( p < 0.01 for all groups). Total EOM to orbit CSA ratios were reduced for 21 patients (87.5%); this was statistically significant in 13 patients (54.2%). There was significant improvement in CAS, proptosis, diplopia, and EOM motility ( p < 0.01 for all categories). There was a significant correlation between reduction of EOM CSA, and reduction of diplopia ( p < 0.01) and EOM motility ( p < 0.01). EOM CSA is significantly reduced following treatment with teprotumumab, and correlates with clinical findings including improvement in extraocular motility and diplopia.

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 2 concentrations of Bupivacaine (5mg/ml and 7.5mg/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 5mg/ml (Group B5, 10 eyes) or 7.5mg/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 3 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 > .05). On comparison to conventional surgery, conjunctival inflammation and hyperaemia, foreign body reaction, and adhesions were less after bupivacaine injection (p >.05 for all except for intensity of conjunctival inflammation in B5 versus conventional surgery). Scleral inflammation was more frequent after bupivacaine injection (p <.05). Muscle fibrosis was more frequent in group B7 and conventional surgery than in group B5 (p >.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.

Diffusion Tensor Imaging Technology to Quantitatively Assess Abnormal Changes in Patients With Thyroid-Associated Ophthalmopathy.

ObjectiveWe aim to investigate the feasibility of using diffusion tensor imaging (DTI) to evaluate changes in extraocular muscles (EOMs) and lacrimal gland (LG) in patients with thyroid-associated ophthalmopathy (TAO) and to evaluate disease severity.Materials and MethodsA total of 74 participants, including 17 healthy controls (HCs), 22 patients with mild TAO, and 35 patients with moderate-severe TAO, underwent 3-Tesla DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) of the EOMs and LG. Ophthalmological examinations, including visual acuity, exophthalmos, intraocular pressure, and fundoscopy, were performed. FA and MD values were compared among patients with different disease severity. Multiple linear regression was adopted to predict the impact of clinical variables on DTI parameters of orbital soft tissue.ResultsTAO patients’ EOMs and LG showed significantly lower FA values and higher MD compared to HCs’ (P < 0.05). Moderate-severe TAO patients’ EOMs and LG had dramatically lower FA and higher MD compared with HCs (P < 0.05). In addition, only the DTI parameters of the medial rectus were considerably different between mild and moderate-severe TAO patients (P = 0.017, P = 0.021). Multiple linear regression showed that disease severity had a significant impact on the DTI parameters of orbital soft tissue.ConclusionDTI is a useful tool for detecting microstructural changes in TAO patients’ orbital soft tissue. DTI findings, especially medial rectus DTI parameters, can help to indicate the disease severity in TAO patients.

Microarray Data of Lacrimal Gland Implicates Dysregulated Protein Processing in Endoplasmic Reticulum in Graves' Ophthalmopathy.

Graves’ ophthalmopathy (GO) has become one of the most common orbital diseases. Although some evidences announced the potential mechanism of pathological changes in extraocular muscle and orbital adipose tissue, little is known about that in lacrimal enlargement of GO patients. Thus, gene expression profiles of lacrimal gland derived from GO patients and normal controls were investigated using the microarray datasets of GSE105149 and GSE58331. The raw data and annotation files of GSE105149 and GSE58331 were downloaded from Gene Expression Omnibus (GEO) database. Bioinformatics including differentially expressed genes (DEGs), Gene Ontology, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network construction, hub gene identification, and gene set variation analysis (GSVA) were successively performed. A total of 173 overlapping DEGs in GSE105149 and GSE58331 were screened out, including 20 up-regulated and 153 down-regulated genes. Gene Ontology, KEGG and GSVA analyses of these DEGs showed that the most significant mechanism was closely associated with endoplasmic reticulum (ER). Moreover, we identified 40 module genes and 13 hub genes which were also enriched in the ER-associated terms and pathways. Among the hub genes, five genes including HSP90AA1, HSP90B1, DNAJC10, HSPA5, and CANX may be involved in the dysfunction of protein processing in ER. Taken together, our observations revealed a dysregulated gene network which is essential for protein processing in ER in GO patients. These findings provided a potential mechanism in the progression of lacrimal enlargement in GO patients, as a new insight into GO pathogenesis.

Correlation of Automated Computed Tomography Volumetric Analysis Metrics With Motility Disturbances in Thyroid Eye Disease.

The authors sought to examine relationships between CT metrics derived via an automated method and clinical parameters of extraocular muscle changes in thyroid eye disease (TED). CT images of 204 orbits in the setting of TED were analyzed with an automated segmentation tool developed at the institution. Labels were applied to orbital structures of interest on the study images, which were then registered against a previously established atlas of manually indexed orbits derived from 35 healthy individuals. Point-wise correspondences between study and atlas images were then compared via a fusion algorithm to highlight metrics of interest where TED orbits differed from healthy orbits. Univariate analysis demonstrated several correlations between CT metrics and clinical data. Metrics pertaining to the extraocular muscles-including average diameter, maximum diameter, and muscle volume-were strongly correlated (p < 0.05) with the presence of ocular motility deficits with regards to the superior, inferior, and lateral recti (with exception of superior rectus motility deficits being mildly correlated with muscle volume [p = 0.09]). Motility defects of the medial rectus were strongly correlated with muscle volume, and only weakly correlated with average and maximum muscle diameter. The novel method of automated imaging metrics may provide objective, rapid clinical information which may have utility in prevention and recognition of visual impairments in TED before they reach an advanced or irreversible stage and while they are able to be improved with immunomodulatory treatments.

Radiological Staging of Thyroid-Associated Ophthalmopathy: Comparison of T1 Mapping with Conventional MRI.

Background Accurate staging of patients with thyroid-associated ophthalmopathy (TAO) is crucial for clinical decision. Full cognition of pathologic changes and staging TAO using conventional T2-weighted imaging is still limited. Purpose To investigate the feasibility of using T1 mapping to evaluate changes of extraocular muscles (EOMs) in TAO patients, as well as to compare T1 mapping and conventional T2-weighted imaging in staging TAO. Materials and Methods Forty TAO patients were retrospectively enrolled. “Hot spot” and “cold spot” T1 relaxation times (T1RTHS and T1RTCS) of EOMs, as well as conventionally applied highest signal intensity ratio (SIR) of EOMs, were measured and compared between active and inactive groups. Results T1RTCS and SIR were significantly higher in active TAOs than in the inactive ones (P < 0.001), while T1RTHS was not (P=0.093). Meanwhile, T1RTCS and SIR were positively correlated with clinical activity score (r = 0.489, 0.540; P < 0.001). TIRTCS and SIR showed no significant area under curve for staging TAO (0.830 vs. 0.852; P=0.748). T1RTCS ≥ 1000 alone showed optimal staging specificity (90.0%), while integration of T1RTCS ≥ 1000 and SIR ≥ 2.9 demonstrated optimal staging efficiency and sensitivity (area under curve, 0.900; sensitivity, 86.0%). Conclusions Our findings suggest that the T1-mapping technique holds the potency to be utilized in TAO. The derived T1RTCS of EOMs, which may be associated with fat infiltration, could be a useful biomarker to stage the disease, serving added efficiency, sensitivity, and specificity to single usage of conventional SIR.

Endocrine ophthalmopathy: pharmacogenetic markers of efficiency of glucocorticoid therapy

The pathological process of endocrine ophthalmopathy is based on damage to the soft tissues of the orbit against the background of impaired thyroid function and even its euthyroid state. The pathogenetic mechanisms of the development of clinical symptoms of endocrine ophthalmopathy (EOP) are based on morphological changes in extraocular muscles (EOM) and orbital tissue: cellular tissue infiltration by representatives of the immune system (T- and B-lymphocytes, macrophages, mast and plasma cells), with the production of pro-inflammatory cytokines, fibroblasts and glycosaminoglycans, contributing to an increase in the contents of the orbit in volume with the development of exophthalmos and tissue fibrosis at the end of the inflammatory process. Glucocorticoids are the gold standard for the pathogenetic treatment of patients with clinical forms of endocrine ophthalmopathy: edematous exophthalmos and endocrine myopathy. The properties of drugs of this group are such that they can be used to suppress all stages of inflammation in the orbital tissues, preventing the progression of the disease. Despite the many years of experience in applying various glucocorticoid therapy techniques, to date there are no uniform criteria for the effectiveness of this treatment in patients with endocrine ophthalmopathy. The article presents the features of glucocorticoid therapy of endocrine ophthalmopathy, as well as literature data, on the basis of which attempts have been made to explain the causes of glucocorticoid resistance taking into account the pharmacogenetic profile.

Thyroid-Associated Orbitopathy: Evaluating Microstructural Changes of Extraocular Muscles and Optic Nerves Using Readout-Segmented Echo-Planar Imaging-Based Diffusion Tensor Imaging.

ObjectiveWe aimed to investigate the ability of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in assessing the microstructural change of extraocular muscles (EOMs) and optic nerves in patients with thyroid-associated orbitopathy (TAO) as well as in evaluating disease activity.Materials and MethodsWe enrolled 35 TAO patients and 22 healthy controls (HCs) who underwent pre-treatment rs-EPI-based DTI. Mean, axial, and radial diffusivity (MD, AD, and RD) and fractional anisotropy (FA) of the medial and lateral EOMs and optic nerve for each orbit were calculated and compared between TAO and HC groups and between active and inactive TAO groups. Factors such as age, sex, disease duration, mediation, and smoking history between groups were also compared. Logistic regression analysis was used to evaluate the predictive value of significant variables for disease activity.ResultsDisease duration was significantly shorter in active TAOs than in inactive ones (p < 0.001). TAO patients showed significantly lower FA and higher MD, AD, and RD than HCs for both medial and lateral EOMs (p < 0.001), but not the AD value of lateral EOMs (p = 0.619). Active patients had significantly higher FA, MD, and AD than inactive patients for medial EOMs (p < 0.005), whereas only FA differed significantly in the lateral EOMs (p = 0.018). The MD, AD, and RD of optic nerves were significantly lower in TAO patients than HCs (p < 0.05), except for FA (p = 0.129). Multivariate analysis showed that the MD of medial EOMs and disease duration were significant predictors for disease activity. The combination of these two parameters showed optimal diagnostic efficiency for disease activity (area under the curve, 0.855; sensitivity, 68.4%; specificity, 96.9%).Conclusionrs-EPI-based DTI is promising in assessing microstructural changes of EOMs and optic nerves and can help to indicate the disease activity of TAO, especially through the MD of medial EOMs.

Ultrastructural changes of extraocular muscles in strabismus patients

ABSTRACTStrabismus is an ocular disorder characterized by partial or complete inability to keep eye alignment. It represents a very common ocular problem at ophthalmology clinics worldwide. The current study aimed to show the most encountered ultrastructural changes in extraocular muscles (EOMs) collected from patients with different forms of strabismus. Nine specimens of EOMs were collected from five patients during strabismus correction surgery and processed for light and electron microscopy examinations. Histologically, skeletal muscle fibers in normal EOMs appeared tight and normally arranged with clear striations. In strabismic muscles, the fibers appeared disarranged, and atrophied, swollen and disintegrated in some situations. By transmission electron microscopy, normal EOMs were formed of skeletal muscle fibers with intact basal membrane and sarcolemma, tightly aligned myofibrils with well-arranged sarcomeres, Z line and H zone, and normally distributed mitochondria. On the other hand, strabismic EOMs revealed vacuolation and degeneration of myofibrils, accumulation of lipid droplets, subsarcolemmal inclusions and clustering of mitochondria. EOMs obtained from a Down syndrome patient with V-pattern infantile esotropia showed extensive vacuolation and disintegration of myofibrils, and extra- and intracellular deposition of collagen fibers. Interestingly, some skeletal muscle cells exhibited features of autophagic cell death with a trial of engulfing process by neighboring cells. In conclusion, our study traces some characteristic ultrastructural changes in strabismic EOMs, most notably, extensive vacuolation, clustering of mitochondria, degeneration of myofibrils and autophagic changes. These changes might be emphasized as possibly secondary to strabismus.

Extraocular muscles involvement in patients with thyroid-associated ophthalmopathy

To study morphological features of extraocular muscles in patients with endocrine myopathy taking into account the duration of the disease. A total of 16 patients with thyroid eye disease were included in the study. After a routine ophthalmic examination, they all underwent extraocular muscle surgery and orbital decompression. The biopsy material obtained at surgery was studied histopathologically. Particular morphological changes have been found in muscles of endocrine myopathy patients. Their relationship to disease duration has been also established. Considering endocrine-related morphological changes in extraocular muscles, the favorable period for surgical correction has been defined.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment.

Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Dystrophic changes in extraocular muscles after gamma irradiation in mdx:utrophin(+/-) mice.

Extraocular muscles (EOM) have a strikingly different disease profile than limb skeletal muscles. It has long been known that they are spared in Duchenne (DMD) and other forms of muscular dystrophy. Despite many studies, the cause for this sparing is not understood. We have proposed that differences in myogenic precursor cell properties in EOM maintain normal morphology over the lifetime of individuals with DMD due to either greater proliferative potential or greater resistance to injury. This hypothesis was tested by exposing wild type and mdx:utrophin+/− (het) mouse EOM and limb skeletal muscles to 18 Gy gamma irradiation, a dose known to inhibit satellite cell proliferation in limb muscles. As expected, over time het limb skeletal muscles displayed reduced central nucleation mirrored by a reduction in Pax7-positive cells, demonstrating a significant loss in regenerative potential. In contrast, in the first month post-irradiation in the het EOM, myofiber cross-sectional areas first decreased, then increased, but ultimately returned to normal compared to non-irradiated het EOM. Central nucleation significantly increased in the first post-irradiation month, resembling the dystrophic limb phenotype. This correlated with decreased EECD34 stem cells and a concomitant increase and subsequent return to normalcy of both Pax7 and Pitx2-positive cell density. By two months, normal het EOM morphology returned. It appears that irradiation disrupts the normal method of EOM remodeling, which react paradoxically to produce increased numbers of myogenic precursor cells. This suggests that the EOM contain myogenic precursor cell types resistant to 18 Gy gamma irradiation, allowing return to normal morphology 2 months post-irradiation. This supports our hypothesis that ongoing proliferation of specialized regenerative populations in the het EOM actively maintains normal EOM morphology in DMD. Ongoing studies are working to define the differences in the myogenic precursor cells in EOM as well as the cellular milieu in which they reside.

Sagging Eye Syndrome

Recognition of sagging eye syndrome (SES) as the cause of chronic or acute acquired diplopia may avert neurologic evaluation and imaging in most cases. To determine whether SES results from inferior shift of lateral rectus (LR) extraocular muscle (EOM) pulleys and to investigate anatomic correlates of strabismus in SES. We used magnetic resonance imaging to evaluate rectus EOMs, pulleys, and the LR-superior rectus (SR) band ligament at an eye institute. Patients with acquired diplopia suspected of having SES. We studied 56 orbits of 11 men and 17 women (mean [SD] age of 69.4 [11.9] years) clinically diagnosed with SES. Data were obtained from 25 orbits of 14 control participants age-matched to SES and from 52 orbits of 28 younger controls (23 [4.6] years). Rectus pulley locations compared with age-matched norms and lengths of the LR-SR band ligament and rectus EOMs. Data were correlated with facial features, binocular alignment, and fundus torsion. Patients with SES commonly exhibited blepharoptosis and superior sulcus defect. Significant inferolateral LR pulley displacement was confirmed in SES, but the spectrum of abnormalities was extended to peripheral displacement of all other rectus pulleys and lateral displacement of the inferior rectus pulley, with elongation of rectus EOMs (P < .001). Symmetrical LR sag was associated with divergence paralysis esotropia and asymmetrical LR sag greater than 1 mm with cyclovertical strabismus. The LR-SR band was ruptured in 91% of patients with SES. Widespread rectus pulley displacement and EOM elongation, associated with LR-SR band rupture, causes acquired vertical and horizontal strabismus. Small-angle esotropia or hypertropia may result from common involutional changes in EOMs and orbital connective tissues that may be suspected from features evident on external examination.

Changes of saccadic eye movements in thyroid-associated ophthalmopathy

To establish whether or not the dynamics of saccadic eye movements are significantly changed in patients with different stages of thyroid-associated ophthalmopathy (TAO) and, subsequently, if analysis of saccades could serve as an additional diagnostic tool for early detection of inflammatory activity in TAO. Thirty-seven patients with TAO and 10 age- and gender-matched control subjects were investigated. The patients were divided into four groups according to the stage of the disease: (i) early mild disease (n = 10), (ii) early severe disease (n = 11), (iii) long-standing restrictive disease (n = 10) and (iv) proven auto-immune hyperthyroidism without any signs of TAO (n = 6). Horizontal and vertical saccades with amplitudes of 10°, 20°, 30° and 40° were recorded binocularly using the induction scleral search coil technique. The two main sequence constants V(max) and C were calculated for each eye. Repeated measurement analysis of variance was carried out to test for differences between different gaze directions, eyes and groups. In horizontal saccades, significant differences were found between groups but not between abduction and adduction. In vertical saccades, differences between groups and the interaction between groups and up- and down-gaze saccades were significant. Compared with the control group, analysis of the main sequence curves revealed larger differences in patients of group 3 and 4 than in those of group 1 and 2. Whereas in the control group down-gaze saccades were faster than up-gaze saccades, the opposite behaviour was found in all patient groups. The largest differences were detected among those patients who had no signs of TAO (group 4). In this study, significant saccade differences were detected in all patients with TAO. In contrast to our earlier studies where evaluation of multiple individual saccade parameters did not reveal significant differences, analysis of the main sequence constants and mathematical reconstruction of the main sequence curves turned out to be a sensitive technique for reliable detection of subtle ocular motility changes. Significant differences were detected even in patients with auto-immune thyroiditis where no clinical signs of TAO were apparent.

Magnetic resonance imaging (MRI) demonstrates enhanced vertical rectus contractility in superior oblique (SO) palsy

Introduction: Vertical deviations in SO palsy greatly exceed those explained by loss of SO vertical action alone. We used MRI to seek evidence for causative secondary changes in extraocular muscle (EOM) volume, cross-sectional area, and contractility in SO palsy.

Radiographic Analysis of Extraocular Muscle Volumetric Changes in Thyroid-Related Orbitopathy Following Orbital Decompression

To evaluate radiographic volume changes in extraocular muscles (EOM) following orbital decompression for thyroid-related orbitopathy (TRO). Medical records of 22 orbits in 12 patients undergoing postoperative orbital CT after orbital decompression for TRO were retrospectively reviewed. All orbits demonstrated no signs of clinical reactivation of TRO. EOM volumes were determined by the summation of each EOM's cross-sectional area in the coronal plane of the CT scans and multiplying the sum by the slice thickness. Main outcome measure was a comparison of EOM volumes preoperatively and postoperatively. All orbits demonstrated proptosis reduction postoperatively with a mean of 4.8 mm +/- 2.1 mm (p < 0.0001). The significant increase in the medial rectus muscle (p = 0.0010) postoperatively accounted for the primary change in the postoperative enlargement of total EOM volume (p = 0.028). The medial rectus muscle increased 27% from the preoperative volume. The lateral rectus, superior rectus/levator complex, inferior rectus, and superior oblique muscles did not demonstrate a significant volume increase postoperatively (p = 0.23, 0.21, 0.17, 0.40, respectively). Two patients who underwent unilateral orbital decompression demonstrated EOM enlargement postoperatively in the operative orbit only. There is a significant increase in medial rectus muscle volume postoperatively in orbits undergoing orbital decompression for TRO despite lacking clinical evidence of disease reactivation.