Are adverse events higher among patients with acute optic neuritis prescribed glucocorticoids? A retrospective, longitudinal cohort study.

OBJECTIVE: Optic neuritis (ON) is an acute focal inflammation of the optic nerve routinely treated with glucocorticoids. We aimed to compare adverse events (AE) among glucocorticoid-treated and untreated patients in the real world to guide clinical decision making about treatment tradeoffs. DESIGN: Retrospective, longitudinal cohort study. SETTING: Claims study from a large, private insurer in the USA (2005-2019). PARTICIPANTS: Adults≥18 years old with ≥1 ICD9/10 ON diagnosis with an evaluation/management visit code, and ≥6 months continuous enrolment prior to and following ON diagnosis. INTERVENTION: Glucocorticoid prescription exposure. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was any AE within 90 days of glucocorticoid prescription. Secondary outcome was AE assessment by severity. Generalised estimating equations with logit link assessed relationships between glucocorticoid prescription and AEs. High-dimensional propensity score analyses accounted for potential confounding (eg, sociodemographics and comorbidities). Sensitivity analyses restricted the cohort to high-dose prescriptions (≥100 mg prednisone equivalent, injection/infusion), AEs within 30 days, highly specific ON definition and traditional propensity score match. RESULTS: Of the 14 311 people with 17 404 ON claims, 66.3% were women (n=9481), predominantly White (78.2%; n=9940), with median age (IQR)=48 (37,60) years. Within 90 days of the claim, 15.7% (n=2733/17 404) were prescribed glucocorticoids. The median (IQR) prescription duration=10 (6,20) days. Any and severe AEs were higher among patients prescribed glucocorticoids versus none (any AEs: n=437/2733 (16.0%) vs n=1784/14 671 (12.2%), adjusted OR 1.33 (95% CI: 1.18 to 1.50); severe AEs: n=72/2733 (2.6%) vs n=273/14 671 (1.9%), adjusted OR 1.82 (95% CI: 1.37 to 2.35)). Sensitivity analyses were similar. CONCLUSIONS: Real-world glucocorticoid prescriptions among ON patients were short-term, associated with a 30% relative increase in potentially serious AEs captured within healthcare encounters, including those not previously observed, such as VTE. These results can inform treatment decisions, particularly for ON patients likely to experience only marginal benefits.

Optic neuritis and mydriasis after vaccination: a case report.

BACKGROUND: Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria. CASE REPORT: A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months. CONCLUSION: This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.

Bilateral retrobulbar optic neuritis combined with optic perineuritis associated with atezolizumab treatment for small cell lung carcinoma.

INTRODUCTION: Ocular immune-related adverse events (OirAEs) associated with novel cancer therapies of immune checkpoint inhibitors (ICIs) are emerging. Retrobulbar optic neuritis (ON) combined with optic perineuritis (OPN), associated with atezolizumab, has been rarely reported and has a unique clinical manifestation. CASE DESCRIPTION: A 67-year-old woman was diagnosed with small-cell lung cancer. As maintenance therapy, atezolizumab was administered continuously for 10 cycles for approximately 14 months. One week after the administration of the tenth dose of atezolizumab, the patient experienced a bilateral, successive painless visual decline. The fundus and the retinal nerve fiber layer revealed no abnormalities, but the ganglion cell of the macula disappeared loss. The concentric shrinking of the peripheral visual field of the left eye was noticed. Orbital MRI revealed bilateral optic nerve thickening and peripheral optic nerve sheath enhancement ("tram-track" and "doughnut" signs). Serology, cerebrospinal fluid results, and image examination ruled out common causes of vision decline, and the condition was identified as bilateral retrobulbar ON combined with OPN as a probable atezolizumab-related immune adverse event. Thereafter, atezolizumab was discontinued, and intravenous methylprednisolone pulse (IVMP) (160 mg/day for 5 days) plus intravenous immunoglobulin (20 g/day for 3 days) was administered. The patient's visual function considerably improved after three weeks. CONCLUSIONS: Retrobulbar ON and OPN associated with atezolizumab are rare side effects that are easily overlooked. Immune-related ON has unique features and requires early identification. The primary treatment for optic nerve irAEs is corticosteroids, but this is not standardized and should be used with caution.

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report.

BACKGROUND: Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. CASE PRESENTATION: A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient's clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. CONCLUSIONS: In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.

Optic Neuritis as a Consequence of Long-Term Medical Treatment Using Anastrozole: A Case Report.

BACKGROUND Vision loss secondary to optic neuritis is an uncommon adverse effect of nonsteroidal aromatase inhibitors. There have been few reports in the literature on visual disturbance in patients on long-term treatment with Anastrozole for breast cancer prevention; but none had symptoms worse than blurry vision and/or xerostomia. The present patient had acute onset of right-sided vision loss without other neurologic deficits while using the aromatase inhibitor Anastrozole for breast cancer treatment. CASE REPORT A 69-year-old woman presented to the Emergency Department with approximately 1 month of worsening right eye vision loss that was not associated with any other neurologic deficits or any acute symptoms. The symptom was constant and without alleviating or aggravating factors. After extensive workup with ophthalmologic evaluation, Infectious Disease evaluation, autoimmune tests, brain imaging, lumbar puncture with CSF analysis, and temporal artery biopsy reporting unremarkable results, it was determined that the patient was in an inflammatory state induced by long-term use of Anastrozole, an aromatase inhibitor. CONCLUSIONS The patient's long-term use of Anastrozole likely played a large part in developing right visual disturbance secondary to optic neuritis, as a patient of this age has little risk of developing conditions such as optic neuritis, unilateral loss of vision, and/or autoimmune conditions.

Intravenous Immunoglobulin in the Treatment of Adalimumab-associated Optic Neuritis.

Optic neuritis (ON) is a rare complication of tumor necrosis factor (TNF)-α inhibitors. The autoantibody serostatus, treatment, and outcome of TNF-α inhibitor-associated ON remain unclear. We herein report a 50-year-old woman with ON following adalimumab therapy. The patient presented with decreasing visual acuity of the right eye, quickly diminishing to light perception. Anti-aquaporin-4 (anti-AQP4) and anti-myelin oligodendrocyte glycoprotein antibodies were negative. Adalimumab was discontinued, and intravenous methylprednisolone and intravenous immunoglobulin (IVIg) were administered. However, her visual acuity improved only up to counting fingers. IVIg may be ineffective depending on the pretreatment severity.

Isolated optic neuritis after pembrolizumab administration for non-small-cell lung carcinoma.

PURPOSE: To report a case of isolated optic neuritis associated with pembrolizumab immunotherapy for metastatic non-small cell lung carcinoma. CASE PRESENTATION: A 76-year-old man, with a history of metastatic non-small cell lung carcinoma, presented with vision loss in his left eye for the past week. He had been treated with pembrolizumab for the underlying disease for 2 months. On presentation, best corrected visual acuity was 20/30 in the right eye and 20/200 in the left eye. Fundoscopy revealed optic nerve edema in the left eye. Visual fields examination in right eye revealed an enlarged blind spot and an extended defect in the inferior nasal quadrant. In the left eye a partial superior arcuate defect and an extended defect in the inferior hemisphere was observed. The mean deviation was -12.15 dB in the right eye and -13.70 dB in left eye. Pembrolizumab was withheld and corticosteroids were administered for a total of nine weeks, first intravenously and then slowly tapered orally, resulting in resolution of optic neuritis, restoration of visual acuity and in relative improvement in the visual field defects after 3 months. Calculated Naranjo Nomogram score was 7, indicating a 'highly probable' correlation. CONCLUSIONS: Optic neuritis is a relatively rare immune-related adverse event after exposure to checkpoint inhibitors cancer immunotherapy. Prompt discontinuation of the offending agent and early initiation of corticosteroid therapy is the mainstay of the treatment.

Retrobulbar Optic Neuritis Induced by Pembrolizumab in a Patient with Lung Adenocarcinoma.

Pembrolizumab is a monoclonal antibody with anti-tumor effects. Only a few reports have previously described retrobulbar optic neuritis induced by pembrolizumab. We herein report the case of a 63-year-old man with advanced lung adenocarcinoma who received cisplatin, pemetrexed, and pembrolizumab combination therapy for six months. Following treatment, a visual field test showed a left central scotoma. Imaging studies showed left optic neuritis without brain metastasis. Blood tests showed an elevated serum creatinine level. He was diagnosed with retrobulbar optic neuritis and pembrolizumab-induced renal failure. After receiving corticosteroid treatment, his renal function rapidly improved. The optic neuritis improved somewhat, but it was not adequately resolved.

Defining the disease course of TNFα blockers-associated Multiple Sclerosis.

Tumour Necrosis Factor alpha (TNFα) blockers are common and effective treatments for several autoimmune diseases but can be associated with neuroinflammatory events. We describe the disease course of ten patients who developed CNS demyelinating events while exposed to TNFα blockers. We divided them into two groups: eight patients with Relapsing Multiple Sclerosis and two isolated optic neuritis. In our cohort, TNFα blockers-associated Multiple Sclerosis does not seem to be associated with a more aggressive course and can be managed with MS-specific DMTs, chosen considering the clinical course and the concomitant autoimmune disease. Our findings need confirmation in larger cohorts to further characterize the disease course of TNFα blockers-associated Multiple Sclerosis.

[Fifity years after the identification of the cause of SMON].

SMON (subacute myelo-optico-neuropathy) is toxic neurological disease which had a profound impact on the population in Japan in 1960's. The clinical characteristics of SMON includes an ascending sensory disturbance, spasticity, and visual impairment typically following abdominal symptoms. Infection was first suspected as an underlying cause of this epidemic. The disorder was ultimately attributed to the overuse of clioquinol, based on the analysis of green urine from affected patients and confirmed by the epidemiological surveys and experimental animal studies. The factors that contributed to the prevalence of SMON which remains the worst example of drug-associated toxicity in Japan to date include the conversion of clioquinol from a purely topical agent to an orally-administered drug, dogma associated with drug safety, relatively limited regulation of drug use, an increase in the number of prescriptions due to the availability of universal insurance, as well as the complexity of the associated abdominal symptoms. Periodical examination of the patients diagnosed with SMON continues to this day. As such, it is important to have a better understanding of clioquinol-induced neurotoxicity together with the mechanisms underlying drug susceptibility; we should not permit the memory of this severe and prominent drug-associated toxicity fade from view.

Cranial Nerve Disorders Associated With Immune Checkpoint Inhibitors.

OBJECTIVE: To describe the spectrum, treatment, and outcome of cranial nerve disorders associated with immune checkpoint inhibitor (Cn-ICI). METHODS: This nationwide retrospective cohort study on Cn-ICI (2015-2019) was conducted using the database of the French Refence Center. In addition, a systematic review of the literature (MEDLINE, Scopus, and Web of Science) for records published between 2010 and 2019 was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the search terms cranial nerve or neuropathy or palsy and immune checkpoint inhibitors. RESULTS: Among 67 cases with ICI-related neurologic toxicities diagnosed in our reference center, 9 patients with Cn-ICI were identified (7 men, 78%, median age 62 years [range 26-82 years]). Patients were receiving a combination of anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death 1 (PD-1)/PD-1 ligand (n = 5, 56%) or anti-PD-1 antibodies alone (n = 4, 44%). Cn-ICI involved optic (n = 3), vestibulocochlear (n = 3), abducens (n = 2), facial (n = 2), and oculomotor (n = 1) nerves. Two patients had involvement of 2 different cranial nerves. Treatment comprised corticosteroids (n = 8, 89%), ICI permanent discontinuation (n = 7, 78%), plasma exchange (n = 2, 22%), and IV immunoglobulin (n = 1, 11%). Median follow-up was 11 months (range 1-41 months). In 3 cases (33%), neurologic deficit persisted/worsened despite treatment: 2 optic and 1 vestibulocochlear. Among cases from the literature and the present series combined (n = 39), the most commonly affected cranial nerves were facial (n = 13, 33%), vestibulocochlear (n = 8, 21%), optic (n = 7, 18%), and abducens (n = 4, 10%). Trigeminal, oculomotor, and glossopharyngeal nerves were less frequently affected (total n = 7). CONCLUSION: Cranial nerve disorders can complicate treatment with ICIs. Approximately one-third of the patients had persisting deficits, most frequently involving hearing and vision loss.