Restricted Eye Movements Research Articles

A peculiar case of idiopathic orbital myositis in adolescence

Abstract
 Introduction : Idiopathic orbital myositis, an inflammation localized at the extraocular muscles, is rarely reported in pediatrics. Until now, the prevalence and incidence of orbital myositis remain unknown. This paper aims to report a case of idiopathic orbital myositis in a young girl with headache.
 Case Illustration : A-16-year-old presented with a droopy eyelid of the left eye (LE) and double vision since 1 week before admission. She also experienced swollen eyelid and cluster headache for 5 months with no neurological abnormalities. Ophthalmic examinations showed exotropia with limited eye movement of LE. Ptosis of LE was noted with margin reflex distance 1 (MRD-1) +2 mm, while MRD-1 +6 mm for the right eye. Other examinations were unremarkable with normal funduscopy and negative RAPD. Non-contrast orbital sinus CT-Scan revealed an enlargement of the superior rectus and lateral rectus muscle. The laboratory result showed slight leucocytosis and normal ESR. High-dose intravenous corticosteroid was administered and tapered with oral steroid. The orbital clinical findings showed improvements, better ocular movements, and diminished headache complaints.
 Discussion : As a rare case, the diagnosis of orbital myositis in adolescence can be challenging and requires detailed examination, and proper imaging to exclude other diagnosis such as ophthalmoplegic migraine, infections, malignancies, or congenital lesions (hemangioma). The first-line therapy is a systemic corticosteroid, which well responded in this patient.
 Conclusion : In this patient, intravenous corticosteroid represent an effective treatment. Close monitoring of the disease progression is required after switching to oral therapy to prevent relapse.

Acute acquired comitant esotropia: Current understanding of its etiological classification and treatment strategies

Abstract: Acute acquired comitant esotropia (AACE) is characterized by acute onset of esotropia without limitation of eye movements in children and adults. AACE has been considered relatively rare, and most previous reports were small case series. However, recently, there has been great interest in this disease because of the rapid increase in the number of cases speculated to be related to the use of digital devices. In a growing number of studies, disputes remain regarding its etiology, clinical features, management, and classification. Herein, we review the literature on the history, clinical features, possible etiologic classifications, and treatment strategies for AACE to provide a comprehensive and updated understanding of the disease.

Odontogenic orbital cellulitis: literature review

Introduction: Odontogenic origin is a rare cause (1.3–5%) of cases of orbital cellulitis, but it can lead to very important morbidity such as blindness or thrombosis of the cavernous sinus. It is therefore important to know how to recognize it. Methods: A literature review was performed. The parameters analyzed included age, sex, ethnicity, clinical presentation, imaging to determine orbital involvement, etiology, microbiology, treatment (medical and/or surgical), and final outcome of each case. Chandler's classification was used to classify the different types of cellulitis. Results: Thirty-five cases of odontogenic orbital cellulitis have been described in literature from 1980 to 2022. In 42.9% of cases, the cellulitis corresponded to an intra-orbital abscess (Chandler stage IV). Thrombosis of the cavernous sinus (stage V) was detected in 5.7% of cases. Periorbital edema (100%), ocular or facial pain (82.9%) and limitation of eye movements (82.9%) were the three most common ophthalmological signs. The anamnesis revealed an element pointing to a dental origin in 97.1% of the cases, the two most frequent being a dental avulsion (20%) or an endodontic treatment (14.3%), in days or weeks preceding the onset of symptoms. Imaging was performed on admission in 94.3% of cases. Regarding the most frequently encountered germs, commensal streptococcus of the oral cavity or anaerobic bacteria were found in 25.7% of cases, and coagulase-negative staphylococcus in 22.9% of cases. In 94.3% of cases, broad-spectrum intravenous antibiotic therapy was initiated as soon as the diagnosis was made. The common feature was the use of metronidazole in 51.4% of cases, combined with a third-generation cephalosporin (11.4%) or amoxicillin-clavulanic acid (8.6%). Orbital drainage was necessary in 71.4% of cases to allow resolution of symptoms, associated with drainage of the maxillary sinus in 45.7% of cases. Finally, the treatment allowed a recovery without sequelae in 80% of cases. Discussion: In case of suspected orbital cellulitis, imaging is crucial to confirm the diagnosis, the type of cellulitis and plan the appropriate surgical treatment. The first step of treatment will be the quick start of a broad spectrum intravenous antibiotic therapy, targeting aerobic and anaerobic bacteria. However, it seems imperative to associate a surgical treatment consisting in a first step of an oral drainage and an elimination of the oral infectious source, as well as an orbital drainage whose approach will have been determined by the imaging. Conclusion: Orbital cellulitis is a rare complication of oral cavity infections, but it must be recognized and treated in time to avoid serious morbidity. An early medical and surgical treatment will usually allow good results and a healing process without sequelae.

Combined Use of Magnetization Transfer Ratio and T2-Mapping to Evaluate Extraocular Muscle Pathophysiology in Myasthenia Gravis with Ophthalmoparesis.

Background Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that most frequently affects the extraocular muscles (EOMs), which causes symptoms such as ptosis and restricted eye movement. The EOMs in MG patients are representative of autoimmune inflammatory changes in muscle tissue. Currently, there is no reliable, and sensitive imaging technique for monitoring EOM changes to assist in the evaluation of underlying pathological changes. Methods This study included MG patients treated between March and November 2022 at the First Affiliated Hospital of Sun Yat-sen University. Healthy controls (matched by age and sex) were included. Participants underwent 3.0 T MRI with magnetization transfer imaging (MTI) and T2-mapping to measure the magnetization transfer ratio (MTR) and T2-mapping values in the superior, inferior, medial, and lateral rectus muscles. Comparisons were made between MG patients and healthy controls, and between MG subgroups with and without ophthalmoparesis. Results The MTR and T2-mapping values successfully reflected EOM fibrosis and inflammatory edema in MG patients. MG patients showed significantly higher MTR and T2-mapping values in the EOMs compared with healthy controls. MG patients with ophthalmoparesis exhibited a lower MTR but higher T2-mapping value compared with those without ophthalmoparesis. Combined MTR and T2-mapping values effectively distinguished between MG patients and healthy controls, and between different severities of EOM involvement, with a superior diagnostic accuracy compared with each parameter alone. Conclusion The combination of MTI and T2-mapping MRI techniques can provide key insight into the pathological changes in EOMs in MG patients. This approach enhances early diagnosis and treatment planning, and therefore may improve clinical outcomes.

Orbital blowout fractures: manifestations and missed diagnoses in 207 surgically treated patients.

We aimed to retrospectively measure the incidence of missed orbital blowout fracture diagnosis in primary examinations of patients with surgically treated fractures, to identify the causes of the diagnostic oversight, and to describe the clinical manifestations of the fractures. A retrospective cohort of all patients with unilateral orbital blowout fractures who underwent subsequent surgical fracture reduction at the Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, from January 2011 to July 2021, was gathered. Demographics, fracture type, associated injuries, clinical manifestations, reconstruction indication, diagnostic delay, and causes of fractures were analysed. For statistical analysis, Fisher's exact test, unpaired t-test, and the Wilcoxon Rank Sum were used. Significance was set at P˂0.05. Fracture diagnosis was missed in 26 (13%) of 207 patients: in 40% of patients aged under 18 years and in 10% of patients aged 18 years or over (P=0.005). Suboptimal eye examination was found in 62% of patients with missed fracture and in 13% of those with timely diagnosis (P<0.001). Adjusted odds ratios for missed diagnosis in patients aged under 18 years versus patients aged 18 years and over was 9.3 (95% CI 2.4-35) and in patients with suboptimal versus sufficient eye examination 13.6 (95% CI 5.1-37). More common clinical manifestations in patients aged under 18 years were diplopia or restricted eye movements (P=0.005), pain in eye movements (P=0.010), nausea and/or vomiting (P<0.001), and bradycardia (P=0.014); periorbital haematoma was rarer (P<0.001). Suboptimal eye examination was involved in 62% and misinterpretation of computed tomography images in 50% of missed fractures, together explaining 85% of cases. Orbital blowout fractures are often missed in primary examination, especially in children and adolescents, who also present with subtler clinical manifestations. While the diagnosis can be difficult, appropriate clinical and radiological examination will reveal most cases.

Treatment of Thyroid Eye Disease-Associated Ophthalmopathy and Myopathy With Intraorbital Injection of 5-Fluorouracil and Triamcinolone Acetonide.

The authors report a technique of local application of anti-metabolite and corticosteroid mixture in the orbit for treatment of thyroid orbitopathy with moderate-severe inflammation and muscle involvement. Patients of one orbital surgeon seen between March 2019 and May 2020 with active thyroid eye disease and restrictive strabismus were considered for local treatment of the myopathic component of the disease. A mixture of 1 ml 5-FU 50 mg/ml, 0.25 ml triamcinolone 40 mg/ml, and 1 ml lidocaine 2% is injected through the skin using a 25-gauge, 1.5-inch needle into the orbit adjacent to the affected extraocular muscle. Six patients were treated in the outpatient setting and 3 patients have been treated with this intervention intraoperatively at the time of orbital decompression. One was treated with the mixture reconstituted with hyaluronic acid (Healon GV) to address postoperative medial rectus fibrosis to the medial wall, this mixture was applied topically in the operative field and not injected. All patients had subjective improvement in the eye movement limitation and 2 patients had a change in motility on exam that was temporally correlated to injections. One patient did not disclose high-dose aspirin intake before injection and experienced a retrobulbar hemorrhage immediately following injection which was successfully treated. No complications were noted as a result of the medication itself. The combination of 5-fluorouracil and triamcinolone acetonide for orbital treatment may be a useful adjunct in treating patients with ongoing inflammatory activity, both in the office and in the operating room. The novel combination may optimize ophthalmic outcomes, modifying disease course in some patients.

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy. However, since only three patients from a single family were reported, it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1. Here, using repeat-primed-polymerase chain reaction (RP-PCR) and long-read sequencing, we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1, typically presenting with oculopharyngodistal myopathy. The CGG repeat expansions range from 161 to 669 repeat units. Most of the patients present with ptosis, restricted eye movements, dysphagia, dysarthria, and diffuse limb muscle weakness. Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging. Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles. Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity, suggesting that ribonucleic acid (RNA) toxicity and mitochondrial dysfunction may contribute to pathogenesis. Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

Diagnostic pitfalls in pediatric orbital entrapment fractures

Prompt diagnosis and management of orbital entrapment fractures in the pediatric patient have been advocated. This retrospective study analyzed a cohort of orbital entrapment fractures in pediatric patients with regard to diagnostic pitfalls, treatment and outcomes in a Level I trauma center in Germany.Based on medical records and radiological imaging, patients under the age of 18 years who presented with orbital fractures during 2009–2021 were analyzed. Overall, 125 patients presented with orbital fractures, of whom 29 patients (23.2%) had orbital entrapment fractures. The majority of patients presented with monocle hematoma (n = 23), diplopia (n = 20), and/or restricted extraocular eye movement (n = 14). While all patients with orbital entrapment fractures underwent three-dimensional imaging, 10 radiological reports (34.5%) did not include findings on orbital entrapment fractures. All patients underwent surgical exploration in less than 24 h. In 12 patients, clinical symptoms such as diplopia and restricted ocular elevation were documented upon postoperative evaluation before discharge.Considering the significant proportion of orbital entrapment fractures that are not noted on radiological imaging, prompt clinical examination should be initiated in pediatric patients at risk for orbital fractures. Urgent surgical intervention should be recommended in entrapment fractures.

Clinical and diagnostic profile of Tolosa-Hunt syndrome; a 7-year retrospective observational study.

Tolosa Hunt Syndrome (THS) was first delineated in 1954 and is caused by a granulomatous inflammation in the cavernous sinus, superior orbital fissure or orbit. In this study the different clinical and diagnostic findings of THS are discussed. Case records of patients diagnosed with THS using the International Classification of Headache Disorders 3rd edition criteria from January 2016-July 2022 were considered for the current study. Demographic, Clinical, Laboratory and Radiological data of all patients fulfilling the inclusion and exclusion criteria was collected from the patient case records through the Medical Records Department of BMCRI Super Specialty Hospital. A total of 60 patients were included in the study with mean age with SD, 50.9 years (13.9) and were predominantly male (66.6%). Restriction of eye movements was the most common symptom affecting 31 (51.7%) patients. Oculomotor nerve (IIIrd Cranial Nerve) palsy was the most common nerve palsy, affecting 36 (60%) patients. Contrast enhancing lesions or T2/FLAIR Hyper-intense areas were seen in the Magnetic Resonance Imaging (MRI) of 59 (98.3%) patients. Cavernous sinus involvement, was the most common site of involvement, in 25 (41.6%) of the patients. All patients were treated with intravenous methyl prednisolone injections and responded well. Restriction of eye movements was the most common symptom, along with cavernous sinus being the most common site of involvement in THS. MRI scans are important diagnostic tools for THS.

Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves' orbitopathy: the MicroGO study.

Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis. Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections. GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation. These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.

Misplaced Intracystic Lacrimal Implant- An Unusual Cause of Failed External Dacryocystorhinostomy.

Various techniques of dacryocystorhinostomy (DCR) by an external or endonasal endoscopic approaches are in practice of ophthalmologists and otorhinolaryngologists. The purpose of this paper is to report a case of misplaced intracystic implant in the orbit following external DCR leading to persistence of watering, diplopia and visual diminution. A thirty nine year old female patient presented with recurrent left eye pain, swelling over medial side of the left eye, watering, progressive blurring of vision and diplopia after revision external DCR. The ophthalmology examination revealed bilateral decreased vision, left side restricted extraocular eye movements, sub capsular cataract. The computed tomography dacryocystograph (CT-DCG) revealed tubular foreign body in the extra-conal space abutting the medial rectus with proximal block in the nasolacrimal duct. This is the first reported case of misplaced implant following external DCR in the literature. It may be suggested that patients undergoing intracystic larimal implant shall be on close follow up for such an occurrence later for timely intervention.

Clinicopathological Features and Management of Orbital Cholesterol Granuloma.

To investigate the clinical features, radiographic features, treatment strategies, pathological features, and prognosis of orbital cholesterol granuloma (CG). Twelve patients with orbital CG who were referred to Tianjin Eye Hospital between January 2002 and December 2020 were included in this retrospective case series study. Data collected including patient ophthalmic manifestations, imaging findings, treatment strategies, pathological features, and prognosis were retrospectively reviewed. The patients comprised 10 males and 2 females. The mean age was 34.5 years (standard deviation [SD] = 8.9, median: 36 and range: 16-45 years). Four patients had a history of orbital trauma. The clinical manifestations at the first visit were proptosis (7/12, 58.3%), periorbital or eyelid swelling (6/12, 50%), limitation of eye movement (4/12, 33.3%), ptosis (2/12, 16.7%), and decreased visual acuity (1/12, 8.3%). Computed tomography (CT) showed a nonenhancing, well-circumscribed lesion in the orbit with extensive erosion of the adjacent frontal bone and temporal bone. Magnetic resonance imaging (MRI) showed a nonenhancing mass with intermediate-to-high signal intensity on T1- and T2-weighted images. Ten patients underwent lateral orbitotomy, and two patients underwent supraorbital orbitotomy. All patients had aggressive bone erosion. Histopathologic evaluation of the cyst contents and wall revealed cholesterol clefts, multinucleated giant cells, histiocytes, foamy macrophages, and altered blood pigments. The mean follow-up time of 79.6 months (SD = 49.8, range: 19-193 months). Three patients were lost to follow-up. No postoperative diminution of vision was noted, and no recurrence was observed. CGs can present as superotemporal or temporal orbital lesions. The diagnosis can be established based on CT and MRI. Most of the patients can have no history of orbital trauma.

The effect of previous orbital decompression on outcomes of rectus muscle recession surgery in patients with thyroid ophthalmopathy

To evaluate the effect of previous orbital decompression on outcomes of rectus muscle recession surgery in patients with thyroid-associated ophthalmopathy. This retrospective study enrolled 55 eyes of 33 patients treated in our hospital for restrictive strabismus caused by thyroid-associated ophthalmopathy. We performed muscle recession for the obviously restricted extraocular muscles, with 6 weeks of follow-up. Surgical outcomes were compared between the orbital decompression group (DG, n=15) and non-orbital decompression group (NDG, n=18). A total of 33 patients with Graves' ophthalmopathy who underwent rectus muscle recession surgery were included. Of these, 15 patients had undergone orbital decompression prior to strabismus surgery, and 18 had not. The two groups did not differ in terms of the preoperative horizontal or vertical ocular deviation, degree of restriction of eye movement, degree of diplopia, or mean number of muscles that underwent surgery (P>0.05). There was no significant difference in the preoperative horizontal or vertical ocular deviation, level of eye movement restriction, degree of diplopia and the success rate of the surgery (P>0.05). Rectus muscle recession surgery in patients with thyroid-associated ophthalmopathy during the quiescent period could improve the ocular deviation and diplopia, and orbital decompression performed before strabismus surgery had no significant effect on surgical technique or outcomes of rectus muscle recession surgery.

A challenging diagnosis of narcolepsy type 2 in a patient with Duane syndrome

Duane syndrome is a form of congenital strabismus with horizontal eye movement limitation. This may present a diagnostic challenge when assessing for rapid eye movements during stage REM utilizing PSG or MSLT. We present a case of a child with Duane syndrome who presented with excessive daytime sleepiness and underwent evaluation for hypersomnia. His eye movement limitation provided a challenge in identifying stage REM. In patients with eye movement limitations or prosthetic eyes, it is necessary to look for other features of stage REM such as low chin EMG tone and EEG pattern.

Teprotumumab-trbw as a Novel Monoclonal Antibody for Thyroid Eye Disease: A Literature Review.

Thyroid eye disease (TED) can cause disfigurement and vision loss, most commonly in patients with Graves' disease.These symptoms are related toorbitalinflammation subsequently cause proptosis and limited eye movement. Traditionally, TED is treated with corticosteroidsto decrease inflammation and surgery once the disease stabilizes. However, multiple medications that play a role in immune modulation have been tested and found to be beneficial in treating TED, either as an adjuvant to steroids or in severe disease resistant to steroids. Teprotumumab-trbw, a novel monoclonal antibody sold under the trade name Tepezza®, is the first immune modulator to be approved by the Unites States Food and Drug Administration (FDA) for TED. Teprotumumab-trbw targets the insulin-like growth factor-1 receptor, which is upregulated onorbitalfibroblasts and decreases activation in patients with TED. The FDA approved this drug for patients with less than nine months of disease duration and high levels of disease activity. Multiple studies have shown significant positive results in disease modulation, as well as limited side effects.

Rhino-orbital Mucormycosis in an Immunocompetent Pediatric Patient, Resembling an Orbital Mass- a Case Report

Rhino-orbital mucormycosis in an immunocompetent pediatric patient can present as an orbital mass. We report a 9-year-old male that presented with periorbital swelling and limitation of left eye movement from one month ago. The patient was treated at another center with a diagnosis of mucormycosis but was referred due to worsening symptoms. Orbital and paranasal sinus CT scan revealed opacities in the left paranasal sinus and soft tissue density in the medial and inferior orbital wall. The patient underwent orbitotomy and mass debulking surgery on suspicion of a possible neoplastic mass. Pathologic evaluations revealed mucormycosis. After receiving intravenous liposomal amphotericin-B that was followed by oral posaconazole syrup for two months and sinus debridement, the symptoms regressed. In immunocompromised pediatric patients, mucormycosis should be considered in the differential diagnosis of an orbital mass.

A study on epidemiology, clinical profile, management, and outcome of Covid-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital in Tamil Nadu

: The main objective of the study is to estimate determine the patient demographics, comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management of COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM).: A descriptive cross-sectional study was conducted among 50 patients admitted and suspected with Mucormycosis in 3 months duration from May 21 to July 21 Covid pandemic at a tertiary hospital in Villupuram. Written informed consentwas taken from patients or nearest of kin. This study was approved by Institutional Ethical Committee of Villupuram.: 84% patients among suspected mucormycosis were found to be diabetic, with 70% being males and 61.9% had covid history either covid positive or post covid status. About 60% of suspected mucor cases had h/o oxygen treatment and almost 44% had h/o steroid treatment for their covid treatment. Clinically 40% had extraocular muscle involvement in the form of restricted eye movement to total ophthalmoplegia and mortality was ranging from 37.5-57.14%. Those with proper glycemic control and initiation of treatment at appropriate time with endoscopic sinus debridement and antifungal therapy showed better recovery.: The study reveals that COVID-19 associated Mucormycosis has risen dramatically due to interplay of uncontrolled diabetes and in-appropriate corticosteroid use leading to pathogenic invasion and adverse outcomes. The infection has caused high morbidity and mortality among covid positive than post covid patients. It could be minimized by strict diabetic control under appropriate insulin dosage, wise use of steroids/oxygen and timely intervention based on clinical evaluation rather than waiting for investigations could minimize the complications from the infection and shorten the hospital stay.

Identification of novel compound heterozygous mutation in Niemann-Pick disease type C gene (P14-11.006)

<h3>Objective:</h3> To report a novel compound heterozygous mutation in two siblings with Niemann-Pick disease type C who displayed distinct phenotypic presentation <h3>Background:</h3> Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disease with heterogenous neurological and systemic manifestations. The vast majority of cases (95%) are caused by mutations in the Niemann–Pick C1 protein (NPC1), whereas the reminder of cases are attributed to mutations in Niemann–Pick C2 protein (NPC2). <h3>Design/Methods:</h3> Case report <h3>Results:</h3> <h3>Case 1:</h3> A 57-year-old female presented with a 5-year history of progressive slowness, poor coordination, and cognitive decline. This was followed by generalized stiffness and recurrent ballistic movements within two years of onset. Her poor postural stability lead to frequent falls. Initial neurological evaluation revealed severe dysarthric speech, moderate vertical eye movement limitation, spasticity and exaggerated deep tendon reflexes, along with dystonic movements. She progressed rapidly, developing generalized dystonia which made her bedbound. <h3>Case 2:</h3> the young sibling of case 1, presented at the age of 56 with 8-year history of poor balance. Symptoms were slowly progressive, noted initially with changes in his balance, slurred speech, and poor coordination. He was also noticed to have mild cognitive changes. Examination revealed cerebellar dysarthria, with failure to generate saccades from primary position downwards. Deep tendon reflexes were brisk, with no evidence of muscle wasting, or spasticity. He showed signs of mild axial and appendicular ataxia. The progression was slow, and he maintained his mobility without requiring walking aids. Molecular genetic testing revealed compound heterozygous mutation in the NPC1 gene; c.180G&gt;T (p.Gln60His) and c.3173C&gt;A (p.Ala1058Asp). All biochemical results were within normal range. Brain MRI showed generalized cerebral and cerebellar volume loss few years into the onset of symptoms in both patients. <h3>Conclusions:</h3> Our report highlights the high intrafamilial heterogeneity and poor genotype-phenotype correlation in the case of Niemann–Pick disease type C. <b>Disclosure:</b> Dr. Abusrair has nothing to disclose. Dr. Amorelli has nothing to disclose. Justyna Sarna has nothing to disclose.

E015 A case of ocular myasthenia gravis seen by rheumatology as suspected mononeuritis multiplex in an adult male shortly after Pfizer-BioNTech SARS-CoV-2 vaccination

Abstract Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of new-onset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARS-COV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link. Disclosure A. Storrie: None. R.M. Hum: None. J. Lilleker: None. P. Ho: None.

Saga of primary myxoid liposarcoma of the orbit

A 24-year-old female presented with proptosis and limitation of eye movements and was investigated radiologically with a tentative diagnosis of lymphangioma. Initial biopsy was considered to be in favor of optic glioma on histopathology, but immunohistochemistry was negative for Glial fibrillary acidic protein (GFAP). A year later, the patient reported back with worsening proptosis. She underwent exenteration of left eye for a posterior mass encasing the optic nerve. The final diagnosis of myxoid liposarcoma was rendered on excision biopsy. The difficulties experienced in establishing diagnosis are shared in this case report.