Metastasis of small cell lung cancer to bilateral extraocular muscles: a case report.

BACKGROUND: Orbital metastasis is a possible complication of small cell lung cancer and a pattern of bilateral invasion of the extraocular muscles has rarely been reported in literature. CASE PRESENTATION: A 46-year-old white male with a past medical history of smoking and stage IV small cell lung carcinoma presented with loss of vision and pain in the left eye. Examination revealed bilateral proptosis and left afferent pupillary defect, and visual acuity was hand motion on the left eye and 4/10 on the right eye. An orbital computed tomography scan showed a compression of the left optic nerve between the extraocular muscles at the apex, and a lateral canthotomy was performed for a new-onset compressive optic neuropathy, with residual visual improvement. There was also significant enlargement of the extraocular muscles in the right orbit. The patient was maintained in palliative treatment with both chemotherapy and local medical and surgical (amniotic membrane cover for exposure keratopathy) ophthalmological treatments until he eventually died 5 months after. CONCLUSION: Bilateral metastasis to the extraocular muscles is a very rare manifestation of small cell lung cancer and the palliative treatment in these cases is challenging.

Combining the Tunnel Orbicularis Oculi Muscle Flap Technique With Skin Grafting for Enhanced Adhesion in Burn-Induced Ectropion Repair.

PURPOSE: Scar contracture of the eyelid following facial burns often has adverse consequences. Total cicatricial contracture often makes adjustment flap translation challenging to implement. Previously used upper and lower eyelid adhesion methods are ineffective for patients with severe cicatricial contracture, and ectropion can easily recur. This study aimed to retrospectively examine upper and lower eyelid adhesions using an orbicularis oculi muscle flap and verify its stability. METHODS: In patients with ectropion caused by severe scar contracture following head and face burns, we employed a tunnel orbicularis oculi muscle flap technique, which involved creating a tunnel between the skin and the tarsal plate of the eyelid, mobilizing the orbicularis oculi muscle, and rotating it into this tunnel to provide stable adhesion of the upper and lower eyelids. Full-thickness skin grafting was then performed. The eyelids were examined postoperatively to determine whether reoperation was necessary and to monitor for any potential complications. RESULTS: This study included 26 patients and 46 eyes. No accidental disconnection occurred after eyelid adhesion, which lasted for an average of 21.87 ± 10.08 months before the eyelid adhesion was cut open. No complications or adverse reactions occurred, and the adhesions did not break unexpectedly. CONCLUSIONS: Repairing eyelid ectropion with the tunnel orbicularis oculi muscle flap is a simple procedure that immediately creates tension against upper and lower eyelid contractures, providing long-term stable adhesion. This method avoids structural disorders, such as eyelid margin scarring, minimally influences surrounding tissues, and has few postoperative complications. It holds great value for repairing eyelid tissue defects and warrants further study.

A Magnetic Actuator Device for Fully Automated Blinking in Total Bidirectional Eyelid Paralysis: First Proof of Concept in a Human Participant.

Purpose: Currently, no solution exists to restore natural eyelid kinematics for patients with complete eyelid paralysis due to loss of function of both the levator palpebrae superioris and orbicularis oculi. These rare cases are prone to complications of chronic exposure keratopathy which may lead to corneal blindness. We hypothesized that magnetic force could be used to fully automate eyelid movement in these cases through the use of eyelid-attached magnets and a spectacle-mounted magnet driven by a programmable motor (motorized magnetic levator prosthesis [MMLP]). Methods: To test this hypothesis and establish proof of concept, we performed a finite element analysis (FEA) for a prototype MMLP to check the eyelid-opening force generated by the device and verified the results with experimental measurements in a volunteer with total bidirectional eyelid paralysis. The subject was then fitted with a prototype to check the performance of the device and its success. Results: With MMLP, eye opening was restored to near normal, and blinking was fully automated in close synchrony with the motor-driven polarity reversal, with full closure on the blink. The device was well tolerated, and the participant was pleased with the comfort and performance. Conclusions: FEA simulation results conformed to the experimentally observed trend, further supporting the proof of concept and design parameters. This is the first viable approach in human patients with proof of concept for complete reanimation of a bidirectionally paretic eyelid. Further study is warranted to refine the prototype and determine the feasibility and safety of prolonged use. Translational Relevance: This is first proof of concept for our device for total bidirectional eyelid paralysis.

Deep-Learning Based Automated Segmentation and Quantitative Volumetric Analysis of Orbital Muscle and Fat for Diagnosis of Thyroid Eye Disease.

Purpose: Thyroid eye disease (TED) is characterized by proliferation of orbital tissues and complicated by compressive optic neuropathy (CON). This study aims to utilize a deep-learning (DL)-based automated segmentation model to segment orbital muscle and fat volumes on computed tomography (CT) images and provide quantitative volumetric data and a machine learning (ML)-based classifier to distinguish between TED and TED with CON. Methods: Subjects with TED who underwent clinical evaluation and orbital CT imaging were included. Patients with clinical features of CON were classified as having severe TED, and those without were classified as having mild TED. Normal subjects were used for controls. A U-Net DL-model was used for automatic segmentation of orbital muscle and fat volumes from orbital CTs, and ensemble of Random Forest Classifiers were used for volumetric analysis of muscle and fat. Results: Two hundred eighty-one subjects were included in this study. Automatic segmentation of orbital tissues was performed. Dice coefficient was recorded to be 0.902 and 0.921 for muscle and fat volumes, respectively. Muscle volumes among normal, mild, and severe TED were found to be statistically different. A classification model utilizing volume data and limited patient data had an accuracy of 0.838 and an area under the curve (AUC) of 0.929 in predicting normal, mild TED, and severe TED. Conclusions: DL-based automated segmentation of orbital images for patients with TED was found to be accurate and efficient. An ML-based classification model using volumetrics and metadata led to high diagnostic accuracy in distinguishing TED and TED with CON. By enabling rapid and precise volumetric assessment, this may be a useful tool in future clinical studies.

Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

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.

Blink Lagophthalmos in Graves Orbitopathy.

PURPOSE: To investigate the relationship between the kinematics of spontaneous blinks and the anterior area of the levator palpebrae superioris muscle in patients with Graves orbitopathy (GO). METHODS: This is a case-control study. The authors measured the margin reflex distance of the upper eyelid (margin reflex distance 1), the kinematics of spontaneous blinks, and the anterior area of levator palpebrae superioris muscle in CT coronal scans of patients with Graves upper eyelid retraction (GO) and a control group. The eye with the greatest margin reflex distance 1 was selected for analysis in each group. RESULTS: A total of 68 participants were included, with 36 in the GO group and 32 in the control group. In the GO group, the mean margin reflex distance 1 measured 6.5 mm, while in the control group, it was 3.9 mm. Almost all parameters related to the closing phase of spontaneous blinking activity, including amplitude, velocity, blinking rate, and interblink time, did not differ between the two groups. However, the effectiveness of the blink's amplitude (ratio of blink amplitude to margin reflex distance 1) and the main sequence (relationship between amplitude and velocity) were significantly reduced in the GO group compared with the control group. The area of the levator palpebrae superioris muscle was significantly larger in GO than in controls, with 71.4% of patients' muscles outside of the maximum range of the controls. CONCLUSIONS: In patients with GO, there is a reduction in blinking effectiveness, also known as blink lagophthalmos, which is a factor in the common occurrence of ocular surface symptoms. The increase in velocity with amplitude is also reduced in GO.

Surgical Management of Overgrowth Syndrome With Bilateral Vision-Threatening Ptosis.

We describe the first case reported in ophthalmological literature of the surgical management of a 17-month-old boy with bilateral vision-threatening ptosis, tarsomegaly, ectropion, and euryblepharon secondary to suspected overgrowth syndrome. We elaborate on the major challenges associated with surgical management including the natural and asymmetric growth of oversized tissue, the high likelihood of scarring and formation of disorganized tissue, and risks of frequent intubation in these patients who may have lesions that compromise critical structures such as the airway. Ultimately, surgical intervention is encouraged primarily if vision or ocular health is threatened and secondarily to achieve good cosmesis.

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease.

PURPOSE: This study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED). STUDY DESIGN: Retrospective study. METHODS: The thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses. RESULTS: The TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement. CONCLUSIONS: TSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED.

Developmental, Physiological and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of sarcomeric myosin heavy chains (MyHCs) that they express and changes in MyHC expression during phylogeny. Myogenic progenitors from the mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles (EOMs) express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB (nmMyH IIB). They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC and cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift toward expressing slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs that they express. Thyroid hormone shifts MyHC 2A toward 2B in jaw muscles, laryngeal muscles and possibly extraocular muscles. This review highlights the fact that the pattern of myosin expression in mammalian craniofacial muscles is principally influenced by the complex interplay of cell lineages, neural impulse patterns, thyroid and other hormones, functional demands and body mass. In these respects, craniofacial muscles are similar to limb muscles, but they differ radically in the types of cell lineage and the nature of their functional demands.

Normative measurements of orbital structures on magnetic resonance images; a cross-sectional study with mini review of the literature.

PURPOSE: Awareness of normative values of extra orbital structures would provide useful information to interpret the radiological images better and use them for diagnostic purposes. This study aimed to reveal the average values of major extraocular structures measured on magnetic resonance images. METHODS: In this retrospective cross-sectional study, magnetic resonance (MR) images of 256 orbits of 128 patients were re-interpreted regarding the measurements of major orbital structures. Extraocular muscles, superior ophthalmic vein, and optic nerve-sheath complex were measured on orbital MR images of these patients. The data distributions were presented by box-plot analyses for each parameter, and the measurement results were analyzed regarding gender and age groups. RESULTS: Lateral rectus muscle thickness (LR), inferior rectus muscle thickness (IR), globe position (GP), and interzygomatic line (IZL) values were higher in the male group than in the female group (p values were < 0.001, 0.003, 0.020, and < 0.001 respectively). LR, the thickness of the superior group muscles (SUP GR), IR, superior oblique muscle thickness (SOBL), and the thickness of optic nerve-sheath complex (ON) values indicated a significant relationship between age groups. There was a significant, positive, and low-level correlation between age and LR, SUP GR, and IR values (p values were < 0.001, 0.001, and < 0.001, respectively). CONCLUSION: This study provides quantitative data on normative values of orbital structures with gender and age group comparisons. Clinicians or surgeons can easily use the measured values to gather diagnostic information from the orbital region.

Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

BACKGROUND AND OBJECTIVES: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03049956.

Long-term surgical outcome and impact on daily life activities of strabismus surgery in thyroid-associated ophthalmopathy with and without previous orbital decompression.

BACKGROUNDS: To report the long-term surgical outcomes and the impact on daily life activities of strabismus surgery in patients with Thyroid Associated Orbitopathy (TAO) with and without previous orbital decompression. METHODS: Patients who underwent strabismus surgery for TAO were retrospectively reviewed. The primary outcome was to evaluate the influence of orbital decompression on the outcomes of TAO related strabismus surgery. Surgical success was defined by the resolution of diplopia and a post-operative deviation < 10 prism diopters (PD). The secondary outcomes were the clinical features, surgical approaches, and impact on daily life activities. RESULTS: A total of 45 patients were included in the study. The decompression surgery group (DS) included 21 patients (46.7%), whereas the non-decompression surgery group (NDS) patients were 24 (53.3%). The mean follow-up time from the last strabismus surgery was 2,8 years (range 8-200 months). Successful surgical outcome was achieved in 57,1% of patients in the DS, and 75% of patients in the NDS (p = 0,226). DS patients required almost twice the number of surgical interventions for strabismus compared to the NDS (1,95 vs. 1,16 respectively, p = 0,006), a higher number of extraocular muscles recessed in the first surgery (2,67 vs. 1,08 respectively, p < 0.001), and a lower rate of unidirectional surgery compared to NDS (23% vs. 95%, p < 0,001). At the pre-operative assessment, 71.4% of DS patients had eso-hypotropia, while no patients had this type of strabismus in the NDS group (p < 0.001). On the other hand, the hypotropia rate was 79.2% in NDS patients and only 4.8% in DS patients (p < 0.001). Moreover, 21,8% of NDS patients used prism lenses in daily life activities, compared to 42.9% of patients that used prism lenses to reduce the impairment in their daily life activities (p = 0.016). CONCLUSIONS: The results of our study showed that DS patients required almost twice the number of strabismus surgical procedures, a higher number of extraocular muscles recessed in the first surgery, and an increased need for prism lenses to correct the residual deviation compared to the NDS, but with similar long-term surgical outcomes.

Wearable apparatus for correction of visual alignment under torsional strabismus.

SIGNIFICANCE: A wearable optical apparatus that compensates for eye misalignment (strabismus) to correct for double vision (diplopia) is proposed. In contrast to prism lenses, commonly used to compensate for horizontal and/or vertical misalignment, the proposed approach is able to compensate for any combination of horizontal, vertical, and torsional misalignment. PURPOSE: If the action of the extraocular muscles is compromised (e.g., by nerve damage), a patient may lose their ability to maintain visual alignment, negatively affecting their binocular fusion and stereo depth perception capability. Torsional misalignment cannot be mitigated by standard Fresnel prism lenses. Surgical procedures intended to correct torsional misalignment may be unpredictable. A wearable device able to rectify visual alignment and restore stereo depth perception without surgical intervention could potentially be of great value to people with strabismus. METHODS: We propose a novel lightweight wearable optical device for visual alignment correction. The device comprises two mirrors and a Fresnel prism, arranged in such a way that together they rotationally shift the view seen by the affected eye horizontally, vertically, and torsionally. The extent of the alignment correction on each axis can be arbitrarily adjusted according to the patient's particular misalignment characteristics. RESULTS: The proposed approach was tested by computer simulation, and a prototype device was manufactured. The prototype device was tested by a strabismus patient exhibiting horizontal and torsional misalignment. In these tests, the device was found to function as intended, allowing the patient to enjoy binocular fusion and stereo depth perception while wearing the device for daily activities over a period of several months. CONCLUSIONS: The proposed device is effective in correcting arbitrary horizontal, vertical, and torsional misalignment of the eyes. The results of the initial testing performed are highly encouraging. Future study is warranted to formally assess the effectiveness of the device on multiple test patients.

Asymmetric proptosis in thyroid eye disease.

PURPOSE: Patients with thyroid eye disease (TED) can present with asymmetric disease. The purpose of this study was to evaluate the prevalence of asymmetric TED in an Australian cohort and investigate clinical, biochemical, and radiological associations of asymmetric TED. METHODS: This was a retrospective study of patients with TED who underwent Hertel exophthalmometry and orbital computed tomography (CT) scans. Asymmetry was defined as a difference in the globe protrusion of ≥ 3 mm using Hertel exophthalmometry. Data was collected on patient demographics, clinical disease presentation, thyroid function tests and antibody levels. Muscles volumes were determined by manually segmenting the extraocular muscles on CT scans using a commercially available software. RESULTS: 172 orbits from 86 patients were included in the study. 28 (33%) patients had asymmetric TED. No significant differences were observed in age, gender, thyroid hormone status, anti-thyroid peroxidase levels, thyroid stimulating hormone receptor antibodies, disease activity status, or dysthyroid optic neuropathy between the asymmetric and non-asymmetric groups. The extraocular muscle volumes were significantly higher in the asymmetric orbit compared to its contralateral orbit. CONCLUSION: Asymmetric TED is a reasonably common occurrence in the course of TED. It is associated with higher extraocular muscle volumes, suggesting muscle enlargement as one of the underlying contributors to asymmetric proptosis. Thyroid eye disease should be considered in the differential of asymmetric orbital inflammatory disease.

[The timing and challenges of early intervention for infantile esotropia].

Infantile esotropia is a common ophthalmic disease in children. A lot of clinical and basic research evidence suggests that early surgery enhances sensory and ocular motor development. However, the proper timing of surgery has been debated for decades. In addition, there is more likely instability of deviation in the preoperative evaluation of infants, and even if the patient achieved alignment after surgery, the defects in binocular vision may accompany for a lifetime. This article analyzes the difficulties and key points of early intervention for infantile esotropia, aiming to provide scientific ideas for the early treatment of children with infantile esotropia in China.

Surgery for longer duration supranuclear ophthalmoplegia secondary to brain stem cavernoma: A case report and literature review.

BACKGROUND: Previous reports revealed that patients with acquired paralytic strabismus caused by central nervous system diseases are primarily affected by the etiology and treatment of the condition. Strabismus correction for these acquired paralytic strabismus should be performed as soon as the primary disease has been stabilized for 6 months in order to archive a favorable surgical outcome. CASE: We followed an infrequent case of longer-lasting supranuclear ophthalmoplegia secondary to brain stem cavernoma. OBSERVATION: A 25-year-old Chinese Han female developed aberrant head posture and ipsilateral conjugate gaze palsies 8 years after the first brainstem hemorrhage caused by pontine cavernoma. The patient was diagnosed with supranuclear ophthalmic palsy and brain stem cavernoma after surgery. A resection-recession procedure along with a rectus muscle transposition was performed. The patient's abnormal head position disappeared, with a normal primary position. CONCLUSION: Resection-recession procedures combined with rectus muscle transposition works very well for longer duration large-angle strabismus caused by brain stem cavernoma.