Ophthalmoplegia Associated With Extramedullary Multiple Myeloma: Case Series From a Tertiary Cancer Center.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder of plasma cells that results in tumor cells replacing the bone marrow. In extramedullary MM (EMM), however, tumor cells proliferate outside the bone marrow. EMM may produce ophthalmoplegia through direct invasion of the superior orbital fissure, cavernous sinus, and/or sphenoidal sinus. Several mechanisms have been proposed including cranial nerve palsies, direct infiltration of bone, extraocular muscle metastasis, myelomatous meningitis, and parenchymal or paraneoplastic effects. METHODS: We retrospectively reviewed the medical records of 7 patients at MD Anderson Cancer Center who suffered from ophthalmoplegia secondary to extramedullary MM between 2019 and 2021. We collected information regarding the symptoms, signs, radiographic and laboratory findings, management, complications, and prognosis of these patients throughout their disease course. RESULTS: Skull base MRI revealed 4 patients with ophthalmoplegias secondary to superior orbital fissure invasion, 2 patients with ophthalmoplegias secondary to cavernous sinus invasion, and 1 patient with ophthalmoplegia secondary to sphenoid sinus invasion. CONCLUSIONS: This is a case series describing 7 patients with ophthalmoplegias secondary to EMM. Our article is unique because of the size of the included cohort, which is large when compared with most English language publications detailing such ophthalmoplegias.

Optic nerve biopsy in leukemic infiltrative optic neuropathy: a case report and review of the literature.

Optic nerve infiltration is a rare but known complication of the central nervous system (CNS)-involving lymphoma and leukemic disorders. The diagnosis is often presumed and patients are empirically treated with systemic therapy and/or local radiation. Optic nerve biopsy is usually avoided due to the risk of permanent vision loss secondary to the procedure. We present a case of biopsy-proven leukemic optic neuropathy without optic nerve sheath or cerebrospinal fluid (CSF) involvement in a patient previously in remission from T-cell prolymphocytic leukemia (T-PLL). To our knowledge, this is the first documented case of T-PLL with biopsy-proven optic nerve invasion without CSF involvement and suggests possible perineural invasion or a sanctuary site from chemotherapy. We suggest that for patients with poor vision and suspected leukemic infiltration without other evidence of CNS involvement, both optic nerve and optic sheath biopsy should be performed for diagnosis and treatment.

Overview of Ocular Side Effects of Selinexor.

BACKGROUND: The aim of this review is to elucidate the type and frequency of ocular adverse events associated with selinexor with a goal to quantify the occurrence of these events in our investigator-initiated trial. METHODS: We retrospectively reviewed medical records of 174 patients treated with at least one dose of selinexor in combination with multiple standard chemotherapy or immunotherapy agents between July 2015 and July 2020 at a comprehensive cancer center in the U.S. All reported ocular adverse events were assessed. RESULTS: A total of 174 patient medical records were reviewed. All patients received at least one dose of selinexor in combination with multiple standard chemotherapy or immunotherapy agents in our cohort of patients with advanced malignancies. A total of 34 (19.54%) patients experienced 37 ocular adverse events. The most frequently reported ocular symptom was blurred vision, which was reported in 22 (12.64%) patients. The most frequently reported treatment-related adverse event was dry eye syndrome reported in 21 (12.1%) patients, and 19 (10.9%) of them were diagnosed with mild dry eye. The second most common treatment-related adverse event was the progression of age-related nuclear sclerosis (cataract) reported in 7 (4.0%) patients. None of the ocular adverse events required therapy discontinuation. CONCLUSION: Our findings highlight that ocular adverse events associated with oral selinexor were mild. The most frequently reported ocular treatment-related adverse events were mild dry eye and progression of age-related nuclear sclerosis. None of the ocular adverse events required therapy discontinuation. IMPLICATIONS FOR PRACTICE: Patients receiving selinexor in combination with multiple standard chemotherapy or immunotherapy agents were reviewed, with a total of 34 patients experiencing 37 ocular adverse events. Findings highlight that ocular adverse events associated with oral selinexor were mild. The most frequently reported ocular treatment-related adverse events were mild dry eye and progression of age-related nuclear sclerosis. None of the ocular adverse events required therapy discontinuation.

Immune-Related Oral, Otologic, and Ocular Adverse Events.

Emerging immunotherapeutic agents, including immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1), have revolutionized cancer treatment. The first immune checkpoint inhibitor (ICI) ipilimumab, an anti-CTLA-4, was approved in 2011. Since then, the US Food and Drug Administration (FDA) has approved more than half a dozen immune checkpoint inhibitors to treat various malignancies. These agents are part of a broader class of chemotherapy agents termed immunotherapy, which selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. While the effects of traditional chemotherapy are well known, the toxicity profile of emerging immune therapies is not fully elucidated. They have been associated with atypical side effects labeled collectively as immune-related adverse events (irAEs).

Immune-Related Oral, Otologic, and Ocular Adverse Events.

Emerging immunotherapy agents, such as immune checkpoint inhibitors, have shown remarkable promise in the treatment of various malignancies. These drugs selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. Due to the novelty of these therapeutic agents, their toxicity profile is less well understood.Meta-analysis results reveal that the overall prevalence of oral mucositis, stomatitis, and xerostomia is lower with checkpoint inhibitors compared to conventional chemotherapy, and head and neck radiation therapy. However, the widespread use of immunotherapy reveals new oral mucosal barrier adverse events, including bullous pemphigoid, mucous membrane pemphigoid, and lichenoid mucositis. Audiovestibular dysfunction can occur from autoimmune-mediated pathways of immunotherapy (adoptive cell) with limited treatment options. Such auditory complications can lead to speech recognition deficits and sensorineural hearing loss. Ocular toxicities are among the most common adverse events resulting from the use of these agents. The majority of ocular immune-related adverse events (irAEs) are mild, low-grade, non-sight threatening, such as blurred vision, conjunctivitis, and ocular surface disease. Serious and sight-threatening events, including corneal perforation, optic neuropathy, and retinal vascular occlusion, can occur but are infrequent. In this chapter, we review the current evidence on the clinical manifestations of oral, audiovestibular, and ocular immune-related adverse events (i.e., irAEs).

Neuro-ophthalmologic features of chordoid glioma.

Chordoid glioma is a rare intracranial tumor typically arising in the third ventricle, particularly along the anterior aspect of the hypothalamic wall. We describe the clinical, neuroimaging, and pathologic factors of this neoplasm in a patient presenting with a chiasmal syndrome.

Transverse and Sigmoid Sinus Dural Arteriovenous Fistula Mimicking Idiopathic Intracranial Hypertension and Carotid Cavernous Fistula.

Intracranial dural arteriovenous fistulas (dAVFs) can produce a variety of symptoms depending on fistula location, size, and venous drainage. Although cavernous sinus fistulas (CCFs) classically present with symptoms of orbital venous congestion due to retrograde venous drainage into the superior ophthalmic vein (i.e. an arterialised "red eye") (Miller NR. Neurosurg Focus 2007;23:1--15), dAVFs not localised to the cavernous sinus rarely present with a "red eye" and instead produce increased intracranial pressure, which can mimic idiopathic intracranial hypertension (IIH). The authors present a unique case of an intracranial dAVF with clinical features suggestive of both CCF and IIH. Clinicians should be aware of this possibility to avoid delayed diagnosis of the intracranial dAVF.

Cup-to-Disc Ratio in Idiopathic Intracranial Hypertension without Papilloedema.

This study seeks to characterise potential differences in the cup-to-disc ratio (CDR) of patients with idiopathic intracranial hypertension (IIH) with papilloedema (IIHWP) compared with IIH without papilloedema (IIHWOP). The medical charts, optical coherence tomography (OCT), and digital optic disc photos of 30 patients (59 eyes) with IIHWP and 4 patients (8 eyes) with IIHWOP were reviewed retrospectively. The CDR values of the two groups were analysed using the Wilcoxon-Mann-Whitney test. Results showed a statistically significant smaller CDR in patients with IIHWP as compared with IIHWOP. These findings suggest that structural factors of the optic disc may play a role in the development of or lack thereof of papilloedema in patients with IIH.

Immune checkpoint monoclonal antibody-related adverse effects in neuro-ophthalmology.

Immunotherapy has renovated the field of oncology. Usually, cancer is treated by surgery, chemotherapy, and radiation. Immunotherapy is a promising treatment that harnesses the patient's own immune system to target cancer. Immune checkpoint inhibitors (ICIs) have proven to be a promising treatment avenue for managing cancer; however, their use had been associated with a unique spectrum of adverse side effects called immune-related adverse events (irAEs). As ICIs become increasingly relevant in cancer management, it is crucial to address these irAEs affecting various systems in the body, including the skin, liver, gastrointestinal tract, endocrine system, and the eye. Ocular toxicity and sight-threatening events are among the reported irAEs, impacting diverse ocular tissues. The most commonly reported ocular irAEs (OirAEs) are blurred vision, conjunctivitis, ocular surface disease uveitis, scleritis, and retinopathy. Nevertheless, the frequency and severity of these OirAEs can vary, even within the same class of ICIs. Thus, OirAEs can significantly impact the quality of life and patient compliance. Therefore, we aim to comprehensively analyze uncommon and severe ICI-related OirAEs associated with lung cancer by providing a comprehensive and updated review of immune checkpoint monoclonal antibody-related adverse effects in neuro-ophthalmology irAEs. Through a review of the relevant literature, we intend to illustrate the epidemiology, clinical characteristics, contributory factors, diagnosis, and management of ICI-associated ocular side effects. We will also discuss guidelines and best practice strategies for the prevention, monitoring, and management of these OirAEs.

Incidence of Ophthalmological Complications in NF-1 Patients Treated with MEK Inhibitors.

MEK inhibitors (MEKi) represent innovative and promising treatments for managing manifestations of neurofibromatosis type 1 (NF1). To mitigate potential ophthalmic side effects, such as MEKi-associated retinopathy (MEKAR), patients undergoing MEKi therapy routinely receive ophthalmology evaluations. Our study aims to assess the necessity of this regular screening within a predominantly pediatric NF1 population by examining the occurrence of ocular adverse events (OAE). A retrospective study evaluated 45 NF1 patients receiving MEKi. Inclusion criteria included baseline and follow-up examinations following the initiation of MEKi therapy. At each assessment, a comprehensive eye evaluation was performed, comprising a dilated fundus examination, ocular coherence tomography of the macula and nerve fiber layer, and Humphrey visual field testing. Twenty-six patients, with an average age of 13 years (range 2-23 years) and an average follow-up duration of 413 days were included in the analysis. Three different MEKi were used: selumetinib (77%), trametinib (23%), and mirdametinib (4%). None of the patients experienced retinopathy at any point during the study. Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication.

Conjugal giant cell arteritis.

While the pathogenesis of giant cell arteritis (GCA) remains unclear, a number of factors may be contributory, including genetic, environmental, and immune. There have been few reports of GCA occurring in a conjugal pair, all originating from Northern Europe or the Northern United States. We document GCA occurring in a husband and wife from the southern Gulf Coast of the United States and discuss the implications of this, as well as the current understanding of the pathogenesis of GCA.

Immunoglobulin G4-positive Sclerosing Idiopathic Orbital Inflammation: New Neuro-ophthalmological Presentations.

We report two rare cases of biopsy proven Immunoglobulin G4-related sclerosing orbital inflammation (IgG4SOI). The first case had intracranial involvement which, to our knowledge, is the first IgG4SOI case with serum cerebrospinal fluid abnormalities and the second case had an unusual presentation of a compressive optic neuropathy and systemic lymphadenopathy.

An Uncommon Case of Multiple, Recurrent Cerebrospinal Fluid Venous Fistulas.

We present a clinical case to discuss the use of computed tomography (CT) spine myelograms alongside a complete history to diagnose multiple cerebrospinal fluid (CSF) venous fistulas (CVFs). The goal of this study is to familiarize clinicians with this challenging diagnosis and the utility of these studies in localizing leaks. A 63-year-old male patient with a history of cervical spinal stenosis, intermittent double vision, and sinus pressure managed with intermittent steroids presented to the clinic. He provided a detailed timeline of his previous symptoms and previous workups leading to the suspicion of intracranial hypotension due to CSF leak vs. CVF. Our workup, including magnetic resonance imaging (MRI) of the cervical spine and lumbar puncture (LP), was conducted. A CT thoracic spine myelogram was completed to localize the fistula site which was followed by the embolization of the fistula. The patient revealed complete resolution of his symptoms confirmed by imaging done one week postoperatively. This was a difficult case complicated by chronic misdiagnosis and confounding factors. CVFs were first described less than a decade ago; however, they are an extremely important cause of spontaneous intracranial hypotension. CVFs can be challenging to detect on conventional anatomical imaging like MRI. Thus, CT myelogram studies and a thorough history are crucial for accurate diagnosis. It is essential that clinicians, including ophthalmologists, learn to recognize CVFs as a potential cause of intracranial hypotension and become familiar with this diagnosis and its workup in the hopes that, unlike this case, the diagnosis and resolution of patients' life-altering symptoms are not delayed.

Primary balloon angioplasty of venous Sinus stenosis in idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH. METHODS: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), comparing clinical outcomes using bivariate analyses. RESULTS: 62 patients were included with median age of 33 [IQR 26-37], 74% females. Group A (9/62) and Group S (53/62) had similar baseline characteristics. Papilledema improvement was higher in Group S at 6 weeks and 6 months (44 vs. 93, p = 0.002 and 44 vs. 92%, p = 0.004), with similar improvements across all symptoms. Group S had higher mean post-procedure venous pressure gradient change (8 vs. 3 mmHg, p = 0.02) and a lower CSF opening pressure at 6 months (23 vs. 36 cmH2O, p < 0.001). VPS rescue rate was higher in Group A (44 vs. 2%, p = 0.001). There was only one procedural complications; a subdural hematoma in Group A. CONCLUSIONS: Primary VSS balloon angioplasty provides a marginal and short-lived improvement of IIH symptoms compared to stenting. These findings suggest a cautious and limited role for short-term rescue angioplasty in poor shunting and stenting candidates with refractory IIH.

Ocular Toxicity Profile of Targeted Cancer Therapy (TCT) at a US Tertiary Cancer Center.

PURPOSE:  Targeted cancer therapy (TCT) is a significant advancement in oncology with promising survival improvement in patients with cancer and remarkable effects on various cancers. There is evidence suggesting a connection between specific TCT classes and the occurrence of immune-related adverse events (irAEs). Our study aims to investigate the potential ocular toxicities of different classes of TCT, provide a better understanding of these toxicities, and aid in the future development of screening and management recommendations for ocular irAEs. DESIGN:  Retrospective observational case series. PARTICIPANTS:  Only ocular immune-related AEs were included in the study; patients on TCT who received a new ophthalmic diagnosis were seen at the MD Anderson Cancer Center. METHODS:  Between 2010 and 2019, we retrospectively reviewed the medical records of 6,354 patients on TCT at a large US tertiary cancer center.  Results: The criteria for data analysis were met by 1861 patients. TCT was associated with a wide range of class-specific ocular irAEs. There was a statistically significant correlation between ocular toxicity with polytherapy with a p-value of <0.001. Furthermore, there was a statistically significant correlation between toxicity and BRAF, epidermal growth factor receptor (EGFR), and ICI <0.001, <0.001, and 0.006, respectively.  Conclusion: Our cohort is the most extensive case series in English literature, demonstrating the increased risk of class-specific ocular toxicity associated with TCT, which sheds some light on the importance of developing standardized grading criteria and management guidelines.

Deformable anatomic templates embed knowledge into patient's brain images: Part 1. Construction and display.

OBJECTIVE: This paper describes the methods used to create annotated deformable anatomic templates (DATs) and display them in a patient's axial 2-dimensional and reformatted volume brain images. METHODS: A senior neuroradiologist annotated and manually segmented 1185 color-coded structures on axial magnetic resonance images of a normal template brain using domain knowledge from multiple medical specialties. Besides the visible structures, detailed pathways for vision, speech, cognition, and movement were charted. This was done by systematically joining visible anatomic anchor points and selecting the best fit based on comparisons with cadaver dissections and the constraints defined on the companion 2-dimensional images. RESULTS: The DAT is commercially available for use on a picture archiving and communication system or as a standalone workstation. CONCLUSIONS: The DAT can quickly embed extensive, clinically useful functional neuroanatomic knowledge into the patient's brain images. Besides labeling visible structures, DAT displays clinically important, previously uncharted subdivisions of the fiber tracts.

Case Report: Neuromyelitis Optica After Treatment of Uveal Melanoma With Nivolumab and Ipilimumab.

The development of immune checkpoint inhibitors (ICIs) has greatly improved survival of patients with advanced malignancies. ICIs can cause immune-related adverse effects (irAEs) involving any organ. Neurological irAEs are infrequent and have mostly been reported in patients with melanoma. We describe the case of a 57-year-old male with right eye uveal melanoma, gene expression profile (class 2), and PRAME (preferentially expressed antigen in melanoma) positivity, who received plaque brachytherapy with Iodine-125 for 4 days with subsequent adjuvant ICIs (immune checkpoint inhibitors), nivolumab and ipilimumab. 18 weeks after discontinuation of immunotherapy, the patient presented with acute onset of left-sided headaches, pain with eye movements, and vision loss. The patient was tested positive for serum anti-aquaporin-4 antibody (AQP4-Ab) and was diagnosed with neuromyelitis optica spectrum disorder (NMOSD). Subsequently, he was treated with 5 days of intravenous methylprednisolone followed by an oral prednisone taper over 10 weeks, with improvement in symptoms. We report a unique case of neuromyelitis optica spectrum disorder (NMOSD) following treatment with ICIs. To our best knowledge, this is the third reported case in English literature of NMOSD following ICI therapy and the first reported case of NMOSD caused by ICI treatment in uveal melanoma.