Peripheral Retinal Haemorrhages in a Patient with MOG-Associated Optic Neuritis.

A 15-year-old female presented with headaches and bilateral vision loss. Fundoscopic examination revealed bilateral optic nerve oedema as well as peripheral retinal haemorrhages. Magnetic resonance imaging of the brain showed findings consistent with bilateral optic neuritis. The patient was started on high dose intravenous corticosteroids but her vision failed to improve. The presence of retinal haemorrhages raised concern that a vasculitis was underlying her symptoms, prompting an extensive work-up, which was unrevealing. Plasmapheresis was initiated and the patient's vision eventually improved to 20/20 in both eyes. Ultimately, she was found to be positive for myelin oligodendrocyte glycoprotein (MOG) antibodies, consistent with a diagnosis of MOG-associated optic neuritis. The patient's course was typical for MOG-associated optic neuritis but her peripheral retinal haemorrhages were atypical, which created diagnostic uncertainty. It is important to be aware of the possibility of retinal findings in this disease. We also review potential causes for retinal haemorrhages in optic neuritis.

Correlation Between Visual Acuity and Foveal Threshold by Automated Perimetry With Size V Stimulus.

BACKGROUND: Visual acuity has been shown to correlate with foveal threshold as determined by automated perimetry. Although automated perimetry with size V stimulus is commonly used in neuro-ophthalmology practice, the relationship between the visual acuity and the foveal threshold with this larger stimulus is not well known. METHODS: Retrospective study of patients who had undergone neuro-ophthalmology evaluation and visual field testing with automated perimetry using size V stimulus. Healthy controls were also recruited. Using visual acuity and foveal threshold, Pearson correlation coefficients were calculated, and basic foveal threshold statistics were stratified by visual acuity. Prediction intervals for visual acuities by various foveal threshold were also calculated. RESULTS: A total of 106 unique eyes were included. The final Pearson correlation coefficient between visual acuities was -0.795 for the right eye and -0.578 for the left eye, with a pooled correlation coefficient of -0.751 (P < 0.001). A foveal threshold of at least 34 dB was present in 94.4% of eyes with 20/20 visual acuity, and a foveal threshold of greater than 35 dB was not observed in eyes with visual acuity of 20/40 or worse. CONCLUSIONS: Foveal threshold as determined by automated perimetry using size V stimulus has moderate-to-strong correlation with visual acuity in patients undergoing neuro-ophthalmology evaluation.

Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy: Demographics, Risk Factors, and Visual Outcomes.

BACKGROUND: Although nonarteritic anterior ischemic optic neuropathy is a well-known cause of vision loss, it typically presents unilaterally. Simultaneous, bilateral nonarteritic anterior ischemic optic neuropathy (sNAION) is rare and poorly studied in comparison. This study seeks to characterize the clinical features and risk factors of patients with sNAION compared with unilateral NAION (uNAION). METHODS: In this retrospective case-control study, we reviewed 76 eyes (38 patients) with sNAION and 38 eyes (38 patients) with uNAION (controls) from 4 academic institutions examined between 2009 and 2020. Demographic information, medical history, medication use, symptom course, paraclinical evaluation, and visual outcomes were collected for all patients. RESULTS: No significant differences were observed in demographics, comorbidities and their treatments, and medication usage between sNAION and uNAION patients. sNAION patients were more likely to undergo an investigative work-up with erythrocyte sedimentation rate measurement ( P = 0.0061), temporal artery biopsy ( P = 0.013), lumbar puncture ( P = 0.013), and MRI ( P < 0.0001). There were no significant differences between the 2 groups for visual acuity, mean visual field deviation, peripapillary retinal nerve fiber layer thickness, or ganglion cell-inner plexiform layer thickness at presentation, nor at final visit for those with ≥3 months of follow-up. The sNAION eyes with ≥3 months of follow-up had a smaller cup-to-disc ratio (CDR) at final visit ( P = 0.033). Ten patients presented with incipient NAION, of which 9 suffered vision loss by final visit. CONCLUSION: Aside from CDR differences, the risk factor profile and visual outcomes of sNAION patients seem similar to those of uNAION patients, suggesting similar pathophysiology.

Misdiagnosis of Third Nerve Palsy.

BACKGROUND: This study identifies the diagnostic errors leading to misdiagnosis of 3rd nerve palsy and to aid clinicians in making this diagnosis. The objective of this article is to determine the incidence of misdiagnosis of 3rd cranial nerve palsy (3rd nerve palsy) among providers referring to a tertiary care neuro-ophthalmology clinic and to characterize diagnostic errors that led to an incorrect diagnosis. METHODS: This was a retrospective clinic-based multicenter cross-sectional study of office encounters at 2 institutions from January 1, 2014, to January 1, 2017. All encounters with scheduling comments containing variations of "3rd nerve palsy" were reviewed. Patients with a documented referral diagnosis of new 3rd nerve palsy were included in the study. Examination findings, including extraocular movement examination, external lid examination, and pupil examination, were collected. The final diagnosis was determined by a neuro-ophthalmologist. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was used to categorize the causes of misdiagnosis. Seventy-eight patients referred were for a new diagnosis of 3rd nerve palsy. The main outcome measure was the type of diagnostic error that led to incorrect diagnoses using the DEER criteria as determined by 2 independent reviewers. Secondary outcomes were rates of misdiagnosis, misdiagnosis rate by referring specialty, and examination findings associated with incorrect diagnoses. RESULTS: Of 78 patients referred with a suspected diagnosis of 3rd nerve palsy, 21.8% were determined to have an alternate diagnosis. The most common error in misdiagnosed cases was failure to correctly interpret the physical examination. Ophthalmologists were the most common referring provider for 3rd nerve palsy, and optometrists had the highest overdiagnosis rate of 3rd nerve palsy. CONCLUSIONS: Misdiagnosis of 3rd nerve palsy was common. Performance and interpretation of the physical examination were the most common factors leading to misdiagnosis of 3rd nerve palsy.

Evaluation of 2D FLAIR hyperintensity of the optic nerve and optic nerve head and visual parameters in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: T2/FLAIR hyperintensity of the optic nerve/optic nerve head has been described as a sensitive finding in idiopathic intracranial hypertension using post-contrast 3D-T2/FLAIR imaging. The purpose of this study is to assess whether hyperintensity on non-enhanced 2D-T2/FLAIR imaging occurs more likely in diseased patients than controls and to evaluate the relationship between FLAIR signal and visual parameters MATERIALS AND METHODS: A retrospective case-control study was performed of patients with idiopathic intracranial hypertension and controls who underwent orbital MRI. Three neuroradiologists reviewed the FLAIR images, subjectively evaluating for hyperintense signal within the optic nerves/optic nerve heads using a 5-point Likert Scale. Quantitative assessment of optic nerve signal using regions of interests was performed. Clinical parameters were extracted. The diagnostic performance was evaluated, and Spearman correlation calculated to assess the relationship between FLAIR signal and visual outcomes. RESULTS: The sensitivity of abnormal FLAIR signal within the optic nerves and optic nerve heads in patients with idiopathic intracranial hypertension ranged from 25-54% and 4-29%, respectively, with specificities ranging from 67-92% and 83-100%. Quantitative assessment revealed a significant difference in CNR between cases and controls in the left posterior optic nerve (p=.002). A positive linear relationship existed between abnormal optic nerve head signal and papilledema grade (OD: p=.02, OS: p=.008) but not with other visual parameters. CONCLUSION: T2/FLAIR hyperintensity in the optic nerve/optic nerve head may support the diagnosis of idiopathic intracranial hypertension but its absence should not dissuade it. If present, abnormal signal in the optic nerve head correlates with papilledema.

Patient Harm Due to Diagnostic Error of Neuro-Ophthalmologic Conditions.

PURPOSE: To prospectively examine diagnostic error of neuro-ophthalmic conditions and resultant harm at multiple sites. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 496 consecutive adult new patients seen at 3 university-based neuro-ophthalmology clinics in the United States in 2019 to 2020. METHODS: Collected data regarding demographics, prior care, referral diagnosis, final diagnosis, diagnostic testing, treatment, patient disposition, and impact of the neuro-ophthalmologic encounter. For misdiagnosed patients, we identified the cause of error using the Diagnosis Error Evaluation and Research (DEER) taxonomy tool and whether the patient experienced harm due to the misdiagnosis. MAIN OUTCOME MEASURES: The primary outcome was whether patients who were misdiagnosed before neuro-ophthalmology referral experienced harm as a result of the misdiagnosis. Secondary outcomes included appropriateness of referrals, misdiagnosis rate, interventions undergone before referral, and the primary type of diagnostic error. RESULTS: Referral diagnosis was incorrect in 49% of cases. A total of 26% of misdiagnosed patients experienced harm, which could have been prevented by earlier referral to neuro-ophthalmology in 97%. Patients experienced inappropriate laboratory testing, diagnostic imaging, or treatment before referral in 23%, with higher rates for patients misdiagnosed before referral (34% of patients vs. 13% with a correct referral diagnosis, P < 0.0001). Seventy-six percent of inappropriate referrals were misdiagnosed, compared with 45% of appropriate referrals (P < 0.0001). The most common reasons for referral were optic neuritis or optic neuropathy (21%), papilledema (18%), diplopia or cranial nerve palsies (16%), and unspecified vision loss (11%). The most common sources of diagnostic error were the physical examination (36%), generation of a complete differential diagnosis (24%), history taking (24%), and use or interpretation of diagnostic testing (13%). In 489 of 496 patients (99%), neuro-ophthalmology consultation (NOC) affected patient care. In 2% of cases, neuro-ophthalmology directly saved the patient's life or vision; in an additional 10%, harmful treatment was avoided or appropriate urgent referral was provided; and in an additional 48%, neuro-ophthalmology provided a diagnosis and direction to the patient's care. CONCLUSIONS: Misdiagnosis of neuro-ophthalmic conditions, mismanagement before referral, and preventable harm are common. Early appropriate referral to neuro-ophthalmology may prevent patient harm.

Failure to Obtain Urgent Arterial Imaging in Acute Third Nerve Palsies.

BACKGROUND: Isolated third nerve palsy may indicate an expanding posterior communicating artery aneurysm, thus necessitating urgent arterial imaging. This study aims to assess the rate and duration of delays in arterial imaging for new isolated third nerve palsies, identify potential causes of delay, and evaluate instances of delay-related patient harm. METHODS: In this cross-sectional study, we retrospectively reviewed 110 patient charts (aged 18 years and older) seen between November 2012 and June 2020 at the neuro-ophthalmology clinic and by the inpatient ophthalmology consultation service at a tertiary institution. All patients were referred for suspicion of or had a final diagnosis of third nerve palsy. Demographics, referral encounter details, physical examination findings, final diagnoses, timing of arterial imaging, etiologies of third nerve palsy, and details of patient harm were collected. RESULTS: Of the 110 included patients, 62 (56.4%) were women, 88 (80%) were white, and the mean age was 61.8 ± 14.6 years. Forty (36.4%) patients received arterial imaging urgently. Patients suspected of third nerve palsy were not more likely to be sent for urgent evaluation (P = 0.29) or arterial imaging (P = 0.082) than patients in whom the referring doctor did not suspect palsy. Seventy-eight of 95 (82%) patients with a final diagnosis of third nerve palsy were correctly identified by referring providers. Of the 20 patients without any arterial imaging before neuro-ophthalmology consultation, there was a median delay of 24 days from symptom onset to imaging, and a median delay of 12.5 days between first medical contact for their symptoms and imaging. One patient was harmed as a result of delayed imaging. CONCLUSIONS: Third nerve palsies were typically identified correctly, but referring providers failed to recognize the urgency of arterial imaging to rule out an aneurysmal etiology. Raising awareness of the urgency of arterial imaging may improve patient safety.

Lumbar Puncture for Diagnosis of Idiopathic Intracranial Hypertension in Typical Patients.

BACKGROUND: Patients with typical features of pseudotumor cerebri syndrome (PTCS) must undergo lumbar puncture (LP) to demonstrate elevated opening pressure and cerebrospinal fluid (CSF) analysis to rule out alternative diagnoses. As LP may be associated with significant morbidity, this study aims to determine its necessity in diagnosing typical PTCS. METHODS: Retrospective chart review at 3 university-based neuro-ophthalmology practices included women aged 18-45 years with body mass index >25, papilledema, negative neuroimaging, and who met criteria for PTCS or probable PTCS. RESULTS: One hundred fifty-six patients were enrolled. Seven (4.5%) had clinically insignificant CSF abnormalities. No diagnoses or management changed based on LP/CSF results. CONCLUSION: LP may not be routinely required in the initial evaluation of typical patients with PTCS evaluated by experienced clinicians We caution, however, that further prospective study is required to determine potential risks and benefits of LP as a tool in the diagnosis of IIH before recommending general practice changes.

Current opinion neurology: visual pathway biomarkers in Alzheimer's disease.

PURPOSE OF REVIEW: The incidence of Alzheimer's disease is increasing. Premortem diagnosis of Alzheimer's disease is now possible but require invasive and expensive testing such as PET amyloid beta binding and/or spinal fluid amyloid beta levels. There is a great need for minimally invasive and inexpensive biomarkers to allow for early diagnosis and intervention. RECENT FINDINGS: There has been a large volume of literature assessing ocular biomarkers for Alzheimer's disease. Much of the research to date has significant limitations, including sample size, variable diagnostic criteria for Alzheimer's disease, lack of biomarker assessment, and focus on patients with well established dementia. Work that is more recent has included individuals with early and preclinical Alzheimer's disease with biomarkers included in the design. These studies have shown consistent features of visual pathway involvement in Alzheimer's disease, even in the earliest and preclinical stages. SUMMARY: It is possible that in the future, ocular biomarkers (particularly retinal imaging techniques) may be part of a multimodality alogorithm screening for preclinical Alzheimer's disease, perhaps combined with other methods, such as blood-based biomarkers.

Developing retinal biomarkers for the earliest stages of Alzheimer's disease: What we know, what we don't, and how to move forward.

The last decade has seen a substantial increase in research focused on the identification, development, and validation of diagnostic and prognostic retinal biomarkers for Alzheimer's disease (AD). Sensitive retinal biomarkers may be advantageous because they are cost and time efficient, non-invasive, and present a minimal degree of patient risk and a high degree of accessibility. Much of the work in this area thus far has focused on distinguishing between symptomatic AD and/or mild cognitive impairment (MCI) and cognitively normal older adults. Minimal work has been done on the detection of preclinical AD, the earliest stage of AD pathogenesis characterized by the accumulation of cerebral amyloid absent clinical symptoms of MCI or dementia. The following review examines retinal structural changes, proteinopathies, and vascular alterations that have been proposed as potential AD biomarkers, with a focus on studies examining the earliest stages of disease pathogenesis. In addition, we present recommendations for future research to move beyond the discovery phase and toward validation of AD risk biomarkers that could potentially be used as a first step in a multistep screening process for AD risk detection.

Identifying Incidence of and Risk Factors for Fluoroscopy-Guided Lumbar Puncture and Subsequent Persistent Low-Pressure Syndrome in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: To explore the incidence of and potential risk factors for developing persistent low-pressure syndrome after lumbar puncture (LP) in patients with idiopathic intracranial hypertension (IIH), as measured by use of blood patches. METHODS: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and LP, comparing them to patients with multiple sclerosis (MS) as controls who also received diagnostic LPs. Demographic, clinical, and radiological data were collected for each patient. The main outcome measure was the rate of post-LP blood patches in IIH patients compared with MS patients. Secondary outcome measures were the likelihood of undergoing an epidural blood patch related to age, body mass index, volume removed, opening pressure, the difference between opening and closing pressure, and the level of puncture within the IIH cohort. RESULTS: One hundred four IIH patients and 149 MS patients were included in the study. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086). Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch. CONCLUSIONS: The incidence of low-pressure syndrome, as measured by blood patches, is similar in IIH patients and MS controls. This suggests that having elevated intracranial pressure before an LP is not protective against developing postpuncture low-pressure syndrome, contrary to common assumptions.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy Complicated by Fatal Cerebral Vasculitis.

A 21-year-old man experienced unilateral vision loss associated with multiple atrophic chorioretinal lesions. He was treated for a presumptive diagnosis of acute retinal necrosis, but his vision did not improve with antiviral therapy. Over the course of several weeks, his symptoms progressed to involve both eyes. The fellow eye showed characteristic yellow-white placoid lesions, prompting treatment with oral corticosteroids for acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Despite high-dose therapy with prednisone 80 mg daily, the patient developed the acute onset of mental status changes within the next several days. Neuroimaging revealed multifocal large-vessel strokes associated with cerebral edema; these infarcts led to herniation and death. Postmortem histopathologic examination confirmed granulomatous inflammation in both ocular and cerebral vasculatures. Together with findings from multimodal imaging obtained throughout this patient's clinical course, our findings support the notion that granulomatous choroiditis is the mechanism of the ocular lesions seen in APMPPE. This granulomatous inflammation can also affect cerebral vessels, leading to strokes.