SARS-CoV-2 Parainfectious Optic Neuropathy: 3 Case Reports and a Review of the Literature.

BACKGROUND: Parainfectious optic neuritis is an inflammatory reaction that occurs shortly after an infection without direct invasion by a pathogen. The clinical profile depends on the infectious organism. Cases of SARS-CoV-2 parainfectious optic neuritis have been reported in the literature, but there are no reviews that have applied strict inclusion criteria to more definitively establish the clinical profile associated with SARS-CoV-2. METHODS: We present 3 new cases of SARS-CoV-2 parainfectious optic neuritis. We also review the literature for definite cases by selecting only those with unambiguous clinical features and MRI findings of optic neuritis, positive SARS-CoV-2 polymerase chain reaction or serology, and the absence of myelin oligodendrocyte-glycoprotein or aquaporin-4 antibodies or other diseases associated with optic neuritis. RESULTS: We report 2 cases of monophasic, unilateral SARS-CoV-2 parainfectious optic neuritis with optic disc edema and nadir visual acuities of finger counting. We report 1 case of mild SARS-CoV-2 parainfectious optic neuritis that featured cotton wool spots, peripapillary wrinkles and hemorrhages, and recurrence after an initial steroid taper. We identified 6 cases of unambiguous SARS-CoV-2 parainfectious optic neuritis from the literature. Combining our case series with the case reports in the literature, the average age was 42.8 years, 3/9 had bilateral disease, 6/8 had optic disc edema, 8/9 had nadir visual acuity of finger counting or worse, and all recovered visual acuity to 20/40 or better after therapy with steroids. CONCLUSIONS: SARS-CoV-2 parainfectious optic neuritis has a clinical profile that is atypical for idiopathic optic neuritis but fairly typical of parainfectious forms of optic neuritis with a severely reduced nadir visual acuity, high likelihood of bilaterality, high incidence of optic disc edema, and prompt and significant response to corticosteroids. Further study with long-term follow-up and epidemiologic investigation will be needed to further characterize this clinical entity.

Telemedicine in neuro-ophthalmology.

PURPOSE OF REVIEW: The COVID-19 public health emergency accelerated the adoption of telemedicine in neuro-ophthalmology. This review surveys the current telemedicine landscape and discusses associated limitations and opportunities. RECENT FINDINGS: Logistic considerations and regulatory changes related to the COVID-19 pandemic have spurred a proliferation of tele-neuro-ophthalmic practice. One significant benefit of telemedicine is increased access to the limited number of neuro-ophthalmologists in the country. Certain elements of the neuro-ophthalmic examination can be ascertained during a video visit or through the use of mobile applications. However, data quality can be limited and more direct evaluation of the fundus currently requires the implementation of imaging techniques, such as fundus photography and/or optical coherence tomography. For cases that require it, a 'hybrid' model can be adopted in which patients physically present to designated locations for testing and subsequently participate in televisit with the physician to discuss the assessment and plan. SUMMARY: Telemedicine provides an alternate pathway for patients to access the limited resource of neuro-ophthalmic care, and it will likely persist beyond the current COVID-19 pandemic. It has some limitations currently but continued progress in technologic, legal, and reimbursement strategies will hopefully facilitate further adoption.

Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events.

BACKGROUND: Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation. METHODS: We report a retrospective, comparative, case-control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking. RESULTS: We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors. CONCLUSIONS: We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.

Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

Spontaneous cerebrospinal fluid leak and idiopathic intracranial hypertension.

PURPOSE OF REVIEW: To review the most recent literature on the relationship of spontaneous cerebrospinal fluid (CSF) leak with idiopathic intracranial hypertension (IIH) and considerations in management of these conditions. RECENT FINDINGS: A link has been proposed between spontaneous CSF leak and IIH based on similar demographics, radiologic, and clinical findings in these patients, and on a plausible mechanism of skull base erosion in the setting of high CSF pressure over time. IIH patients with CSF leak may not present with classic IIH signs and symptoms as the leak can alleviate excess pressure; however, they may develop these after a leak is repaired. There may also be a higher risk of leak recurrence if intracranial hypertension is not treated postoperatively. SUMMARY: A growing body of evidence supports an association between IIH and spontaneous CSF leak. However, this relationship is still not fully elucidated, and there is no current agreement on how to incorporate screening, management, or counseling guidelines for CSF leak into the care of IIH patients. There are also no specific guidelines for evaluation/management of IIH in patients with spontaneous CSF leak. Further interdisciplinary research is needed to explore this connection and to establish screening, evaluation, and management guidelines.

Update on the evaluation of pediatric idiopathic intracranial hypertension.

PURPOSE OF REVIEW: Papilledema associated with idiopathic intracranial hypertension (IIH) may result in irreversible, progressive visual loss. The development of tools for the evaluation of pediatric patients with IIH is particularly relevant as many patients may not be able to comply with the detailed clinical evaluation utilized in adults for the treatment and management of this disease. The purpose of this review is to summarize relevant articles on the diagnostic tools used in evaluation and management of pediatric IIH. RECENT FINDINGS: Studies suggest that characteristic pediatric IIH MRI findings include empty sella turcica, decreased pituitary gland size, optic nerve tortuosity, perioptic subarachnoid space enlargement, posterior globe flattering, and intraocular protrusion of the optic nerve head. On optical coherence tomography (OCT), increased retinal nerve fiber layer and macular thickness may be observed in children with IIH compared with controls. The retinal nerve fiber layer thickness seems to coincide with the severity of papilledema and may be more sensitive than funduscopy for detecting optic nerve head elevation. Research on ultrasound of the optic nerve shows increased size of the optic nerve sheath diameter in pediatric IIH patients, and this may correlate with increased opening pressure on lumbar puncture. SUMMARY: There appears to be characteristic findings on MRI, OCT, and ultrasound studies in pediatric IIH patients. Although ultrasound is rarely used for monitoring these patients nowadays, MRI and OCT can be useful in the evaluation and management of these individuals.

Keeping an eye on dialysis: the association of hemodialysis with intraocular hypertension.

Intraocular hypertension is common during hemodialysis. Dialysis disequilibrium syndrome and intraocular hypertension occur via similar pathophysiologic mechanisms. These mechanisms may contribute to the development of glaucoma and cataracts in a patient population already at high risk for ocular abnormalities, given the common risk factors for chronic kidney disease and impaired aqueous humor outflow. We describe a patient with complicated diabetes mellitus, end-stage renal disease, and recent cataract surgery who developed severe intraocular hypertension during hemodialysis. We recommend increased awareness of the symptoms of intraocular hypertension and subsequent ophthalmologic surveillance in order to prevent long-term visual complications.

Correlation of clinical profile and specific histopathological features of temporal artery biopsies.

BACKGROUND: This study sought to correlate the clinical features of patients with giant cell arteritis (GCA) who present with ophthalmic symptoms and signs, with 2 specific histopathological findings-the presence of giant cells and arterial wall neoangiogenesis. The goal was to assess if these pathological features might be useful in guiding the approach to patient management. METHODS: Medical charts were retrospectively reviewed from 58 patients who underwent a temporal artery biopsy at a single institution. Detailed information was collected about the clinical presentation and course, with an emphasis on visual function. Histopathological and immunohistochemical techniques were used to examine temporal artery biopsies for evidence of inflammation. Correlations were made between the clinical data and the presence of giant cells and neoangiogenesis. RESULTS: Twenty-one (34%) biopsies were positive for inflammation consistent with GCA. Although the percentage of positive biopsies with giant cells was high, neither the presence of giant cells nor neoangiogenesis was predictive of a patient's presenting visual symptoms, severity and bilaterality of vision loss, other ophthalmic manifestations of GCA, presence of headache or jaw claudication, or erythrocyte sedimentation rate. Giant cells were more common in patients with recent weight loss. Immunohistochemistry confirmed diagnoses but did not alter the clinical course or treatment plan. CONCLUSIONS: There was no correlation between the clinical, specifically visual, features of GCA and the presence or absence of giant cells or neoangiogenesis in temporal artery biopsy specimens. Although the presence of neoangiogenesis may be important in the pathogenesis of GCA, our study showed no correlation between this finding and the clinical course.

Shot in the dark.

A 43-year-old woman presented with decreased vision in the right eye associated with painful eye movements 10 days after receiving her first dose of Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine (Pfizer Inc, New York, NY). Two days later she developed painful loss of vision in the left eye. Clinical presentation and magnetic resonance imaging findings were consistent with bilateral optic perineuritis transitioning to optic neuritis. Extensive evaluation including aquaporin-4 immunoglobin G (IgG), myelin oligodendrocyte glycoprotein IgG, and lumbar puncture was unrevealing. Visual acuity at nadir was counting fingers in both eyes, but after receiving intravenous steroids and plasma exchange vision eventually improved to 20/20 in each eye, although she was left with inferior visual field defects and bilateral optic disc pallor. This case highlights the diagnostic challenge in the evaluation of atypical optic neuritis with a review of post-COVID-19 vaccination-associated optic neuritis.

Autoimmune Retinopathy in a Patient with Stiff-Person Syndrome: A Case Report.

PURPOSE: To describe a patient who developed retinal degeneration associated with autoimmune retinopathy (AIR) and who was also found to have anti-glutamic acid decarboxylase (GAD65) autoantibodies and the diagnosis of stiff-person syndrome (SPS). METHODS: Ophthalmologic workup consisted of clinical examination, multi-modality retinal imaging, and electrophysiologic testing. Further neurologic assessment including relevant serum and cerebrospinal fluid studies was also conducted. RESULTS: We highlight the case of a 45-year-old patient who developed subacute, sequential vision loss, along with bilateral lower extremity weakness. On initial presentation, optical coherence tomography (OCT) of the left eye was notable for diffuse attenuation of the outer retinal bands. Fundus autofluorescence demonstrated a ring of hyper-autofluorescence encircling the fovea of the left eye. At fifteen-month follow-up, the right eye also became similarly affected. He was found to have elevated serum and cerebrospinal anti-GAD65 autoantibodies and was diagnosed with both SPS and AIR. CONCLUSION: There is a potential association of anti-GAD65 autoantibodies with the development of AIR.

Blepharospasm in a patient with pontine capillary telangiectasia.

Blepharospasm is rarely due to an identifiable etiology. In the majority of cases, imaging fails to reveal any structural lesion. Here we describe an otherwise healthy patient with blepharospasm who was found to have pontine capillary telangiectasia. We propose a potential association between blepharospasm and pontine capillary telangiectasia.

Clinical and neuroradiologic characteristics in varicella zoster virus reactivation with central nervous system involvement.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS). METHODS: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS. RESULTS: The median age was 71 years [IQR 51.5-76]; 21 (57%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65%); median CSF white blood cell count was 11 [IQR 2-23] cells/µL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29%) CSF and 8/9 (89%) ocular samples. Clinical involvement included the optic nerve in 12 (32%), other cranial nerves in 20 (54%), brain parenchyma in 12 (32%) and spinal cord or nerve roots in 4 (11%). Twenty-seven/28 immunocompetent patients' MRIs were available for review (96%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN. CONCLUSION: OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation.

Magnetic Resonance Imaging Features and Clinical Findings in Pediatric Idiopathic Intracranial Hypertension: A Case-Control Study.

The purpose of this study is to identify salient magnetic resonance imaging (MRI) findings of pediatric IIH, to determine the relevance of these findings with regard to disease pathogenesis, and to relate these findings to the clinical presentation towards identification of risk factors of disease. A retrospective, a case-control study of 38 pediatric patients with and 24 pediatric patients without IIH from the ophthalmology department at a tertiary care center was performed. Clinical data, including ophthalmic findings and lumbar puncture results, were recorded. Neuroimaging, including both MRI and magnetic resonance venography (MRV), was evaluated for perioptic subarachnoid space diameter enlargement, posterior globe flattening, optic nerve head protrusion, empty or partially empty sella turcica, dural venous sinus abnormalities, skull base crowding, and prominent arachnoid granulations. Compared with controls, IIH patients had larger perioptic subarachnoid space diameters, higher incidences of posterior globe flattening, protrusion of the optic nerve heads, an empty sella turcica, and dural venous sinus abnormalities. A perioptic subarachnoid space diameter of ≥5.2 mm was identified as an independent predictor of IIH (p < 0.001) with sensitivity of 87% and specificity of 67%. Several significant MRI findings in pediatric IIH were identified. Using a model that uniquely incorporated clinical and MRI findings at presentation, we provide a framework for risk stratification for the diagnosis of pediatric IIH which may be utilized to facilitate diagnosis. Future prospective work is needed to further validate the model developed in this study.

Glioblastoma multiforme mimicking optic neuritis.

PURPOSE: To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations. OBSERVATIONS: A 48-year-old man presented with decreased vision and pain with eye movements of the right eye. MRI of the brain showed increased T2/FLAIR signal involving the right optic nerve with no other identified abnormalities. He was treated with intravenous steroids for presumed optic neuritis. His visual acuity then rapidly worsened to no light perception, with new orbital apex symptoms including central retinal artery and vein occlusions and inferior division third and fourth nerve palsies. Repeat MRI with contrast showed perineural enhancement surrounding the right optic nerve and markedly reduced diffusion along its entire course. After an unrevealing initial workup and then a 7 month period during which the patient refused follow up, he re-presented with left sided weakness, headache, and confusion. Repeat brain MRI revealed a large mass involving the right optic nerve, optic chiasm, basal ganglia, corpus callosum and brainstem. Biopsy led to a diagnosis of WHO grade IV glioblastoma multiforme. The disease was poorly responsive to temozolomide, bevacizumab and external beam radiation, and the patient passed away 5 months later. CONCLUSIONS AND IMPORTANCE: Malignant optic glioma of adulthood is a challenging diagnosis with a poor prognosis. This rare case highlights the importance of maintaining neoplasm in the differential for optic neuritis masqueraders.

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder.

OBJECTIVE: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. METHODS: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. RESULTS: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). CONCLUSION: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

Neuro-Ophthalmic Disorders in Pregnancy.

The physiologic changes that accompany pregnancy can have important implications for neuro-ophthalmic disease. This article discusses pregnancy-related considerations for meningioma, pituitary disorders, demyelinating disease, myasthenia gravis, thyroid eye disease, idiopathic intracranial hypertension, cerebral venous sinus thrombosis, stroke, migraine, and cranial neuropathies. The article also details the potential neuro-ophthalmic complications of preeclampsia and eclampsia and reviews the use of common diagnostic studies during pregnancy.

Older age and larger cyst size in children with spontaneous rupture of periorbital dermoid cysts.

We analyzed clinical and histopathologic data of 97 pediatric patients who underwent excision of dermoid cysts. On review, 16.5% of the sample population demonstrated localized chronic inflammatory changes, including the presence of giant cells and epithelial disruption. These features were considered indicative of prior cyst rupture. Age at time of initial presentation was significantly older and cyst size was significantly larger in patients with histopathologic signs of previous rupture. Longer time to presentation and time to excision were associated with increased odds of spontaneous rupture.

Complications of Optic Nerve Sheath Fenestration as a Treatment for Idiopathic Intracranial Hypertension.

There are a number of surgical options for treatment of idiopathic intracranial hypertension (IIH) when it is refractory to medical treatment and weight loss. Optic nerve sheath fenestration (ONSF) is one of these options. Use of this procedure varies among centers due to experience with the procedure and concern for associated complications that can result in severe loss of vision. This review summarizes the literature concerning post-surgical complications of ONSF for IIH.

Perioperative Vision Loss after Non-Ocular Surgery.

Perioperative vision loss (POVL) may cause devastating visual morbidity. A prompt anatomical and etiologic diagnosis is paramount to guide management and assess prognosis. Where possible, steps should be undertaken to minimize risk of POVL for vulnerable patients undergoing high-risk procedures. We review the specific risk factors, pathophysiology, and management and prevention strategies for various etiologies of POVL.

A 72-Year-Old Kidney Transplant Recipient With Visual Changes.

A 72-year-old woman with a history of kidney transplant was referred for an eye examination because of visual changes in the left eye. Both optic discs were anomalous in appearance, with central excavation in the left eye greater than the right eye. What would you do next?