Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Morning glory disc anomaly associated with moyamoya disease and pituitary stalk duplication.

Purpose: We report a case of a 10-year-old with Moring glory disc anomaly (MGDA) associated with Moyamoya disease and pituitary stalk duplication. Observations: A 10-year-old Asian child presented with decreased vision in the right eye and bilateral nystagmus. Both dilated fundus exam and magnetic resonance imaging (MRI) of the orbit confirmed MGDA of the right eye. MRI of the brain demonstrated duplication of the pituitary stalk. Magnetic resonance angiography (MRA) of the brain revealed bilateral severe narrowing (greater on the right side) of the distal supraclinoid internal carotid arteries with bilateral reconstitution at the carotid terminus and prominent collaterals, suggestive of Moyamoya disease. Conclusions: Patients with MGDA should undergo neuroimaging due to the associated central nervous system (CNS) anomalies.

Metastatic paraganglioma presenting as ajunctional scotoma.

PURPOSE: To report a unique case of metastatic paraganglioma presenting as a junctional scotoma. OBSERVATIONS: A 38-year-old Caucasian man with a history of abdominal paraganglioma presented with minimally blurred vision 20/25 visual acuity in the left eye. The patient was found to have a junctional scotoma upon visual field testing. Cranial MRI revealed a large peri-clival mass compressing the pre-chiasmal optic nerves and other loci of metastatic disease. Intracranial masses, including metastases, can present with a relatively intact central acuity and nonspecific visual symptoms. CONCLUSIONS AND IMPORTANCE: To the best of our knowledge, this is the first report of metastatic paraganglioma causing a junctional scotoma. In cases with junctional scotoma, careful neuro-ophthalmic assessment and imaging are of paramount importance, even in patients with excellent visual acuity.

Emergent Radiotherapy for Leukemia-Induced Cranial Neuropathies Refractory to Intrathecal Therapy.

Neurologic symptoms from leukemic infiltration of the central nervous system are an oncologic emergency, and expeditious treatment is required to preserve function. We report the case of a 44-year-old patient with relapsed acute myeloid leukemia (AML) who developed sub-acute cranial neuropathies refractory to treatment with intrathecal (IT) chemotherapy. The patient was therefore treated with an emergent course of whole-brain radiotherapy, resulting in immediate improvement and subsequent resolution of cranial neuropathies. This case illustrates that while central nervous system involvement by AML is rare, radiotherapy remains an effective modality to avoid long-term morbidity in patients failing to respond to systemic or IT chemotherapy.

Role of Adjunct Treatments for Idiopathic CSF Leaks After Endoscopic Repair.

OBJECTIVE: A higher incidence of recurrent cerebrospinal fluid (CSF) leaks has been reported with idiopathic CSF leaks. A growing number of institutions advocate for routine use of intracranial pressure-lowering adjunct treatments after endoscopic repair. We report our results in a patient cohort in which only symptomatic patients are subjected to further testing and treatment. STUDY DESIGN: Retrospective review. METHODS: A retrospective review of patients who underwent endoscopic transnasal repair of idiopathic CSF rhinorrhea was performed at the University of Miami, Florida, from July 2010 to July 2017. The database was queried for demographical data, surgical details, radiological findings, and postoperative outcomes. Only patients with greater than a 12-month follow-up were included. RESULTS: Thirty-three patients underwent endoscopic repair of an idiopathic CSF leak. Twenty-six (79%) were females, with an average age of entire study population being 48 years. The average body mass index (BMI) of the cohort was 33 kg/m2 , with 89% being overweight (BMI > 25 kg/m2 ). The skull base defect was found to be mainly at the cribriform plate (64%) and sphenoid sinus (30%). Endoscopic repair was performed successfully as a single repair in 32 patients (97%). The average follow-up was 47 months. Postoperative adjunct medications were used on four patients (12%) with symptomatic idiopathic intracranial hypertension. CONCLUSION: Endoscopic repair of idiopathic CSF leaks was found to have a high rate of success in our study. Postoperatively, only four patients required additional measures to medically reduce symptomatic intracranial hypertension. Routine postoperative adjunct treatments are unnecessary and may expose patients to adverse long-term side effects. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:41-47, 2021.

Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma.

ABSTRACT: An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.

Imaging Characteristics of a Hypervascular Pituitary Spindle Cell Oncocytoma on Magnetic Resonance Imaging and Digital Subtraction Angiography.

BACKGROUND: Spindle cell oncocytomas (SCOs) are rare neuroendocrine tumors of the posterior pituitary that are often misdiagnosed as nonfunctional pituitary tumors. Fewer than 50 cases of SCOs have been described in the literature, and many of these reports have documented the tumors to be hypervascular on imaging or histology. CASE DESCRIPTION: We present the first cerebral angiography imaging findings of an SCO before primary resection. The discovery of a prominent tumor blush, enlarged meningohypophyseal feeders bilaterally, and prominent tumor draining veins aided in preoperative planning and subsequent successful endoscopic transsphenoidal surgical resection. CONCLUSIONS: Despite being a rare entity, SCOs should be included in the differential diagnosis when working up a hypervascular sellar tumor. Flow voids may be present on initial magnetic resonance imaging evaluation. Subsequent digital subtraction angiography can be used to further investigate abnormal vasculature and aid in surgical planning.

Zygomatic dental implant induced orbital fracture and inferior oblique trauma.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.

Subretinal Cysticercosis Extraction With Bimanual, 3-D, Heads-Up-Assisted Pars Plana Vitrectomy: Clinicopathological Correlation and Surgical Technique.

A 16-year-old male presented with blurred vision in the right eye after recent travel to Nicaragua. Funduscopic examination revealed subretinal cysticercosis superior to the optic nerve. The cyst was drained and excised using a bimanual, three-dimensional, heads-up-assisted pars plana vitrectomy without complications. Technical maneuvers for cyst extraction along with clinicopathological correlation are described. Postoperatively, the patient exhibits no signs of recurrence and has excellent vision. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:708-711.].

Idiopathic Unilateral Enlargement of the Extraocular Muscles in an Infant.

A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis. A review of the literature reveals the exceptionally rare nature of this finding. While the authors cannot rule out an atypical case of congenital euthyroid eye disease, this constellation of findings is not consistent with thyroid eye disease and may represent previously described cases of idiopathic enlargement of the extraocular muscles.

Spectral-Domain Optical Coherence Tomography Documentation of Transsynaptic Retinal Degeneration.

Patients with post-geniculate neurologic disease and corresponding visual field loss may have ophthalmologic abnormalities detectable by spectral-domain optical coherence tomography (SD-OCT), presumably by transsynaptic retrograde retinal degeneration. Here, three such patients (ages 13 years through 75 years) illustrate thinning of the macula and ganglion cell complex corresponding to zones of visual field loss. Thinning of the retinal nerve fiber layer is not notable in these patients. SD-OCT may be a useful technique in diagnosing and following patients with post-geniculate neurologic disease. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:768-772.].

Ocular Neuromyotonia Noted after Recent Botulinum Toxin Injection for Sixth Nerve Palsy Following Resection of a Posterior Fossa Skull Base Meningioma.

A 56-year-old female complained of diplopia immediately after surgical excision of a recurrent left skull base tuberculum meningioma. She was found to have a left sixth nerve palsy, which was subsequently treated with botulinum toxin injection to the medial rectus muscle. Three months post injection, the patient had partial recovery of the sixth nerve palsy and new-onset ocular neuromyotonia.

Ventriculoperitoneal shunt as a treatment of visual loss in idiopathic intracranial hypertension.

BACKGROUND: The aims of this study were to evaluate visual function outcomes in idiopathic intracranial hypertension (IIH) patients who underwent ventriculoperitoneal (VP) shunt for visual loss and to determine a VP shunt survival curve over time. METHODS: A retrospective medical record review was performed of all new IIH patients first evaluated at our institution who underwent VP shunt placement over a 7-year period (2004-2010). There were 2 primary outcome measures: the first being visual acuity (VA) and the second being shunt survival. Patients who received VP shunt for visual loss were included in the visual outcome analysis, and all patients who received VP shunt for any reason were included in the shunt survival analysis. RESULTS: Of the 338 new patients with IIH, 19 patients (6%) met the inclusion criteria and 17 underwent VP shunt for visual loss and 2 for headaches. Average follow-up was 21.2 months (range, 5-1,342 days). Of the 17 patients who had VP shunt for visual loss, 5 patients had optic nerve sheath fenestration (ONSF) surgery before VP shunt, and 1 patient had bilateral ONSF surgery after VP shunt. Median VA before shunt was 20/200 in the worse eye (range, 20/20 to NLP) and 20/40 in the better eye (20/20 to HM). Median VA after shunt was 20/60 in the worse eye (20/20 to lumboperitoneal) and 20/30 in the better eye (20/20 to 20/800). The improvement in VA was statistically significant in both worse eyes (P = 0.002, Wilcoxon signed-rank test) and better eyes (P = 0.028). The mean automated visual field (AVF) mean deviation (MD) of available AVFs before shunt was 223.36 dB (range, 233.38 to 27.01 dB) for the worse eye (n = 11) and 219.66 dB (230.11 to 25.91 dB) for the better eye (n = 11). Mean AVF MD deviation of available AVFs after shunt was 220.68 dB (232.13 to 23.97 dB) for the worse eye (n = 11) and 216.35 dB (232.13 to 21.00 dB) for the better eye (n = 11): this improvement was not significant (P = 0.27, P = 0.26, respectively). Independent masked record reviews by 3 neuro-ophthalmologists showed that 9 (53%) patients improved, 5 (29%) unchanged, 1 (6%) worsened, and 2 (12%) were indeterminate. Kaplan-Meier analysis showed a persistent steady decrease of functioning VP shunts over the entire period of 36 months with 80%, 65%, and 48% of VP shunts functioning without replacement, removal, or revision at 12, 24, and 36 months, respectively. CONCLUSION: VP shunts improve or stabilize most IIH patients presenting with severe progressive visual loss or those with visual loss refractive to medical treatment and ONSF. Survival analysis shows persistent decrease of functioning shunts over time.