Objective Diplopia Outcomes for Patients Treated With Teprotumumab for Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease (TED) is a condition caused by inflammatory damage to the periocular tissue that often leads to double vision. Teprotumumab is an insulin-like growth factor 1 receptor antibody that was FDA approved for the management of TED in 2020, although much is yet to be elucidated regarding its effects on diplopia outcomes among patients with TED. Diplopia is a significant and life-altering effect of TED. Previous studies have reported the effect of teprotumumab on double vision subjectively using the Gorman diplopia score. However, there is a gap in the literature addressing the effect of teprotumumab treatment on objective ocular alignment measures. The purpose of our study was to address this gap. METHODS: We performed a retrospective review of patients who were diagnosed with TED, presented with diplopia, and treated with teprotumumab in a single-center academic ophthalmology practice. The primary outcome was change in ocular alignment in primary gaze position at 6 months (completion of teprotumumab treatment). Secondary outcomes included change in ocular alignment in other gaze positions, proptosis, eyelid position, and clinical activity score (CAS) at 6 months compared with baseline. To determine what factors may predict ocular alignment response to teprotumumab, we analyzed baseline characteristics among 3 groups, divided based on whether ocular alignment was worsened, stable, or improved at 6 months. RESULTS: Seventeen patients met inclusion criteria, 3 (18%) worsened, 10 (59%) were stable, and 4 (24%) improved. CAS ( P = 0.02) was significantly different among the groups and was higher in those who worsened and those who improved compared with those who remained stable. Right gaze horizontal prism deviation ( P = 0.01) and left gaze horizontal prism deviation ( P = 0.03) were significantly different among the groups, with a greater degree of left gaze horizontal prism deviation in the worse group than the stable group ( P = 0.04). CONCLUSIONS: Our study demonstrated that most patients remained stable after teprotumumab treatment regarding ocular alignment in primary gaze and the number of patients who improved was slightly higher than the number of patients who worsened after teprotumumab treatment. There are some baseline measures, such as CAS and right and left gaze horizontal prism deviation that can help better predict how a patient will respond to teprotumumab treatment. Our results can better inform physicians of how to counsel patients with TED when considering teprotumumab therapy.

Primary optic nerve sheath schwannoma: a case report.

BACKGROUND: The optic nerve is an unusual site of schwannoma as it lacks Schwannoma cells on it. We report a primary optic sheath schwannoma and to review the literature. CASE REPORT: A 29-year old female presented with progressive painless non-pulsatile proptosis. Ocular examination revealed only axial proptosis. Imaging showed a well-defined intraconal mass abutting optic nerve. A left frontal craniotomy with orbitotomy and tumor excision was done. The tumor was well encapsulated, posteriorly attached to optic nerve without any plane, probable site of origin. The postoperative duration was uneventful without any complications. The histopathology examination confirms the diagnosis of schwannoma. CONCLUSIONS: We suggest to consider orbital optic nerve schwannoma in differential diagnosis of orbital tumors despite its exceedingly rare occurrence.

Transpalpebral transorbital neuroendoscopic (TONES) repair of orbital meningoencephalocele: a technical note.

PURPOSE: Intraorbital encephalocele (OMEC) is a rare entity in adults, usually secondary to an orbital pathology or prior trauma, in particular orbital roof fractures. Treatment of the OMEC is warranted to alleviate the pulsating exophthalmos and prevent potential visual decline. OMEC and orbital roof fractures have been predominantly treated via a craniotomy with a reconstruction of the orbital roof using various implants. With the advances in the endoscopic techniques, neuroendoscopy found its application in the treatment of orbital pathologies. We report a minimally invasive alternative: endoscopic transorbital repair of OMEC. MATERIAL AND METHODS: The repair technique is described with illustrations and clinical images. Narrated operative video demonstrating the procedure is provided. RESULTS: Illustrative case: 50-year-old female presented with progressive right eye proptosis over 6 months. Computed tomography (CT) demonstrated bony erosion in the lateral orbital roof, and magnetic resonance imaging (MRI) showed a small hyperintense T2-weighted and T1-weighted contrast enhancing lesion in the orbit, in the area of the bony erosion. Intraoperatively, the lesion was found to be an orbital encephalocele. The orbital defect was successfully repaired by employing the 'sandwich' technique, in which a dural substitute reinforced with tissue glue were deployed without repair of the osseous orbital roof. The patient tolerated the procedure well with ultimate resolution of proptosis. The cosmetic outcome was excellent. CONCLUSION: The transorbital neuroendoscopic approach (TONES) presents a feasible, minimally invasive alternative treatment option for circumscribed intraorbital encephaloceles with minimal side effects, well tolerated by patients.

Thrombosis of intraorbital arterio-venous fistula.

A 65-year-old male patient presented with a rare arterio-venous fistula (AFV). The symptoms included congestion, decreased visual acuity, and proptosis. Further investigation revealed a non-traumatic intra orbital AFV with ophthalmic vein thrombosis. The management strategy was craniotomy and the prescription of anticoagulants. The patient recovered 2 months after surgery demonstrating successful resolution of his presenting symptoms and an alternative approach to complicated cases of embolization.

Factors Associated with Surgery and Imaging Characteristics in Severe Orbital Infections.

OBJECTIVES: To evaluate risk factors associated with surgical intervention and subperiosteal/orbital abscess in hospitalized children with severe orbital infections. STUDY DESIGN: We conducted a multicenter cohort study of children 2 months to 18 years hospitalized with periorbital or orbital cellulitis from 2009 to 2018 at 10 hospitals in Canada. Clinical details were extracted, and patients were categorized as undergoing surgical or medical-only management. Primary outcome was surgical intervention and the main secondary outcome was clinically important imaging. Logistic regression was used to identify predictors. RESULTS: Of 1579 patients entered, median age was 5.4 years, 409 (25.9%) had an orbital/subperiosteal abscess, and 189 (12.0%) underwent surgery. In the adjusted analysis, the risk of surgical intervention was associated with older age (age 9 to <14: aOR 3.9, 95% CI 2.3-6.6; and age 14 to ≤18 years: aOR 7.0, 95% CI 3.4-14.1), elevated C-reactive protein >120 mg/L (aOR 2.8, 95% CI 1.3-5.9), elevated white blood cell count of 12-20 000/µL (aOR 1.7, 95% CI 1.1-2.6), proptosis (aOR 2.6, 95% CI 1.7-4.0), and subperiosteal/orbital abscess (aOR 5.3, 95% CI 3.6-7.9). There was no association with antibiotic use before hospital admission, sex, presence of a chronic disease, temperature greater than 38.0°C, and eye swollen shut. Complications were identified in 4.7% of patients, including vision loss (0.6%), intracranial extension (1.6%), and meningitis (0.8%). CONCLUSIONS: In children hospitalized with severe orbital infections, older age, elevated C-reactive protein, elevated white blood cell count, proptosis, and subperiosteal/orbital abscess were predictors of surgical intervention.

Erdheim-Chester disease: look it in the eye. An orbital magnetic resonance imaging study.

Erdheim-Chester disease (ECD) is a rare L-group histiocytosis. Orbital involvement is found in a third of cases, but few data are available concerning the radiological features of ECD-related orbital disease (ECD-ROD). Our aim was to characterize the initial radiological phenotype and outcome of patients with ECD-ROD. Initial and follow-up orbital magnetic resonance imaging (MRI) from the patients with histologically proven ECD at a national reference center were reviewed. Pathological orbital findings were recorded for 45 (33%) of the 137 patients included, with bilateral involvement in 38/45 (84%) cases. The mean age (± standard deviation) of these patients was 60 (±11.3) years and 78% were men. Intraconal fat infiltration around the optic nerve sheath adjacent to the eye globe (52%), with intense gadolinium uptake and a fibrous component was the most frequent phenotype described. Optic nerve signal abnormalities were observed in 47% of cases. Two patients had bilateral homogeneous extraocular muscle enlargement suggestive of a myositis-like involvement of ECD-ROD. None had isolated dacryoadenitis but in 17 eyes dacryodenitis was described in association with other types of orbital lesions. Only seven patients (15%) had normal brain MRI findings. ECD-associated paranasal sinus involvement and post-pituitary involvement were detected in 56% and 53% of patients, respectively. A decrease/disappearance of the lesions was observed in 17/24 (71%) of the patients undergoing late (>12 months) followups. Interestingly, ECD-ROD only rarely (7/45; 16%) revealed the disease, with exophthalmos being the most frequently identified feature in this subgroup (3/45; 6%). Even though ECD-ROD can be clinically silent, it comprises a broad array of lesions often resulting in optic nerve signal abnormalities, the functional outcome of which remains to be established. ECD-ROD should thus be assessed initially and subsequently monitored by orbital MRI and ophthalmological follow-up.

Dupilumab as an adjunct treatment for a patient with steroid-dependent immunoglobulin G4-related disease complicated by asthma: a case report.

Introduction: Immunoglobulin G4-related disease (IgG4-RD) responds well to glucocorticoids but is often associated with relapses. Interleukin (IL)-4 and IL-13 are involved in the pathogenesis of IgG4-RD. We present the first case in which dupilumab was an effective adjunct treatment for a patient with steroid-dependent IgG4-RD complicated by asthma.Case study: A 57-year-old man was referred to our hospital for further investigation and treatment of proptosis with neck swelling in 2019. He developed a cough and swelling of the neck in 2016. He was diagnosed with asthma in 2017 and started receiving inhaled glucocorticoids and a long-acting beta-agonist. The patient started receiving oral prednisolone at a dose of 20 mg/day. Oral prednisolone reduced his symptoms, but he relapsed when treatment was tapered to less than 10 mg/day. He was diagnosed with IgG4-RD through a parotid gland biopsy.Results: Azathioprine was given to reduce systemic glucocorticoids. The prednisolone dose was gradually tapered to 10 mg/day, resulting in the relapse of proptosis and an asthma attack. We added dupilumab, and his asthma symptoms and proptosis improved. Serum IgG4 levels continued to decrease, and the prednisolone dose was tapered to 2 mg.Conclusion: Dupilumab might be useful as an adjunctive treatment for patients with steroid-dependent IgG4-RD complicated by asthma. Serum IgG4 levels can be used as a marker to monitor dupilumab treatment in IgG4-RD.

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age.

Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed.

Posttraumatic cerebrovascular injuries in children. A systematic review.

INTRODUCTION: Posttraumatic craniocervical vascular injuries in pediatric traumatic brain injury (TBI) are rare, and children-specific, evidence-based standards on screening and therapy of posttraumatic carotid-cavernous fistula (CCF), craniocervical artery dissections (CCAD), traumatic aneurysms (TA), and posttraumatic sinus venous thrombosis (SVT) is lacking. The aim of this review is to summarize the data on epidemiology, clinical presentation, and treatment of these traumatic lesions in a systematic manner. METHODS: We performed a systematic PubMed search for records of CCF, CCAD, TA, and SVT related to pediatric TBI published until June 2019. RESULTS: After screening 2439 records, 42 were included in the quantitative analysis. Incidences for CCAD in blunt TBI were 0.21% (range 0.02-6.82%). 11.7% (range 1.69-15.58%) of pediatric aneurysms were found to be traumatic of origin, whereas 38.2% (range 36.84-40%) of all pediatric SVT were due to blunt TBI. For all of the posttraumatic cerebrovascular pathologies, we found a clear male predominance with 68.75% in CCF, 63.4% in CCAD, 60% in TA, and 58.33% in SVT. Clinical presentation did not differ from the adult population with exception of young child. While there is only recommendation for the therapy of CCAD and SVT in the pediatric population, no such recommendation exists for the treatment of CCF's and TA's, and data from randomized controlled trials is lacking. CONCLUSION: While these results show that posttraumatic CCF, CCAD, TA, and SVT are rarely encountered in children, misdiagnosis may have potentially drastic consequences due to a longer lifetime burden in the pediatric population. Awareness, early recognition, and prompt initiation of the appropriate therapy are essential to avoid morbidity and mortality. Further studies should focus on the development of clinical and radiological screening criteria of posttraumatic vascular lesions in children.

Odontogenic parakeratinized cyst resulting in exophthalmos and palatine, maxillary, and zygomatic bone erosion in a dog.

A novel case of a canine odontogenic parakeratinized cyst (COPC) that resulted in exophthalmos and palatine, maxillary, and zygomatic bone erosion in a 5-year-old Chihuahua dog is reported. Final diagnosis was aided by cross-sectional imaging (magnetic resonance imaging and computed tomography) and confirmed with histologic examination of the cyst wall.

Exophthalmos due to sterile neutrophilic dermatosis in a dog.

An 8-year-old castrated male Bichon Frise was presented to the Kansas State University Veterinary Health Center for evaluation of unilateral right-sided exophthalmos, suspected secondary to a retrobulbar abscess. The dog had acutely developed right-sided periorbital swelling, exophthalmos with pain on retropulsion, as well as multiple cutaneous exudative plaques on the feet and tail base. On ophthalmic examination, the dog also exhibited mild left-sided exophthalmos with decreased, nonpainful retropulsion. Orbital ultrasound and CT were performed to evaluate the extent of bilateral orbital disease. Incisional biopsies were obtained from the affected right periorbital tissues and skin of the feet, and histopathology revealed severe neutrophilic inflammation of the dermis with no organisms detected. Histologic changes were consistent with sterile neutrophilic dermatosis. The dog achieved clinical remission following treatment with initial immunosuppressive doses of corticosteroids and subsequent long-term maintenance therapy using oral cyclosporine.

[Diagnostic Management of Exophthalmos]. / Leitsymptom Protrusio bulbi ­ diagnostisches Management.

Exophthalmos is a common and important symptom in orbital consultation. It can be either uni- or bilateral. A wide spectrum of benign and malignant diseases has to be considered and evaluated for differential diagnosis, in order to maintain complete ocular function and to lead the patient to adequate therapy. Exophthalmos can be accompanied by variable symptoms, ranging from neurogenic or myogenic to corneal alterations. Symptoms at presentation depend on the underlying disease and may manifest systemically. Interdisciplinary teamwork is essential for diagnostics and therapy of exophthalmos. In addition to ophthalmological routine diagnostics, various supplementary examinations are available which are of importance for disease monitoring. Exact radiological imaging is important for the detailed visualisation of the pathology, surgery as well as treatment planning. Magnetic resonance imaging (MRI) and computed tomography (CT) are the standard imaging techniques used. Contrast enhancement and specific sequences can answer specific problems in detail. Combined positron emission tomography (PET) with CT permits evaluation of metabolic and morphological data and is employed in diagnosis of meningioma, lymphoma and metastases. In summary, the reader should learn important differential diagnoses and accompanying symptoms of exophthalmos, thus enabling essential clinical examinations and adequate imaging.

Choroid Metastasis from Testicular Carcinoma: A Rare Entity.

The aim of this report is to contribute to the clinical understanding of choroid metastasis from testicular carcinoma. A young male patient presented with loss of vision in his left eye with ptosis and proptosis. Fundoscopy revealed bullous retinal detachment with dark hazy vitreous. The preliminary diagnosis of choroid carcinoma with vitreous involvement was made by an ophthalmologist. Later in the physical examination, there was a firm painless left testicular swelling. Testicular tumor markers were raised. Based on ultrasonography, MRI and PET-CT, a clinical diagnosis of left testicular carcinoma metastasizing to the left choroid and vitreous was made. A mixed germ cell tumor was reported on histopathological examination. After cisplatin-based chemotherapy, serum tumor markers normalized and vision improved. Exceptional choroidal and vitreous metastases with absence of other visceral and bony involvement constituted the presenting sign. Although rare, testicular carcinoma must be considered to metastasize to the eye, especially if loss of vision is the chief complaint.

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.

BACKGROUND: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. METHODS: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. RESULTS: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. CONCLUSIONS: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.

[A Case of Subgaleal Hematoma with Exophthalmos and Diplopia].

A 9-year-old girl struck the left side of her head on a doorknob, after which she gradually developed swelling. She was treated conservatively at another hospital before being referred and admitted to our hospital 9 days after injury, with complaints of exophthalmos and diplopia. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) revealed a subgaleal hematoma (SGH). We therefore attempted to treat the patient by aspiration of the hematoma via needle puncture through the skin, for which we wrapped an elastic band around the head while infusing a hemostatic agent. No vascular anomalies and no abnormal shunts were identified by angiography under general anesthesia 13 days after injury. The patient was treated surgically due to increased head swelling and deteriorated exophthalmos. The liquefied, dark-red SGH was aspirated via a few cm of skin and a galeal incision on the left side of her head. A multiperforated drainage catheter was introduced into the hematoma cavity and the drainage catheter was connected to the vacuum-drain pump. After the surgery, the left exophthalmos disappeared. Twenty-three days after injury, she was discharged from our hospital without any neurological deficits.

Hemifacial atrophy.

We report the case of a 44-year-old woman with a one-year history of en coup de sabre morphea and progressive hemifacial atrophy with ipsilateral hemifacial neuralgia, migraine, and contralateral neurologic abnormalities. While rare, Parry-Romberg syndrome typically presents in the first or second decade of life; this patient's case is unusual in that the onset of her disease is demonstrated at age 43. Common clinical features, laboratory findings, and pathogenetic theories are discussed.

Painless Orbital Bone Infarction in a Child with Sickle Cell Anemia: A Case of Misdiagnosed Periorbital Cellulitis.

BACKGROUND Sickle cell orbitopathy is a rare complication of sickle cell disease that closely mimics other conditions, such as orbital cellulitis and osteomyelitis. We report a case of painless orbital bone infarction masquerading as periorbital cellulitis in a child with sickle cell anemia. CASE REPORT A 4-year-old Saudi girl with sickle cell disease presented to our hospital with vaso-occlusive crisis characterized by bilateral lower limb pain and painless left orbital swelling. On examination, she had swelling of the left upper eyelid with redness and mild ptosis (margin reflex distance 1 was 2 mm) without proptosis. Magnetic resonance imaging with contrast showed bilateral sub-periosteal heterogeneous collections (2×0.8×2.1 cm in the superolateral wall of the left orbit and 1×0.6 cm in the inferolateral wall of the right orbit), with intermediate-to-high T1 signal intensity and high T2 signal, causing a mass effect on the adjacent superior and lateral rectus muscles. The patient was treated with systemic antibiotics and supportive treatment for vaso-occlusive crisis under the care of the pediatric team and was discharged without complications. CONCLUSIONS The diagnosis of sickle cell orbitopathy can be challenging, and an accurate diagnosis is essential to ensure appropriate management. Thus, we report the case of a 4-year-old child with painless sickle cell orbitopathy masquerading as pre-septal cellulitis.