A multi-centre case series of patients with coexistent intracranial hypertension and malignant arterial hypertension.

OBJECTIVE: To describe the clinical characteristics, outcomes, and management of a large cohort of patients with concomitant malignant arterial hypertension and intracranial hypertension. METHODS: Design: Retrospective case series. SUBJECTS: Patients aged ≥ 18 years with bilateral optic disc oedema (ODE), malignant arterial hypertension and intracranial hypertension at five academic institutions. Patient demographics, clinical characteristics, diagnostic studies, and management were collected. RESULTS: Nineteen patients (58% female, 63% Black) were included. Median age was 35 years; body mass index (BMI) was 30 kg/m2. Fourteen (74%) patients had pre-existing hypertension. The most common presenting symptom was blurred vision (89%). Median blood pressure (BP) was 220 mmHg systolic (IQR 199-231.5 mmHg) and 130 mmHg diastolic (IQR 116-136 mmHg) mmHg), and median lumbar puncture opening pressure was 36.5 cmH2O. All patients received treatment for arterial hypertension. Seventeen (89%) patients received medical treatment for raised intracranial pressure, while six (30%) patients underwent a surgical intervention. There was significant improvement in ODE, peripapillary retinal nerve fibre layer thickness, and visual field in the worst eye (p < 0.05). Considering the worst eye, 9 (47%) presented with acuity ≥ 20/25, while 5 (26%) presented with ≤ 20/200. Overall, 7 patients maintained ≥ 20/25 acuity or better, 6 demonstrated improvement, and 5 demonstrated worsening. CONCLUSIONS: Papilloedema and malignant arterial hypertension can occur simultaneously with potentially greater risk for severe visual loss. Clinicians should consider a workup for papilloedema among patients with significantly elevated blood pressure and bilateral optic disc oedema.

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.

Diagnostic Error in Neuro-ophthalmology: Avenues to Improve.

PURPOSE OF REVIEW: To highlight potential avenues to reduce preventable diagnostic error of neuro-ophthalmic conditions and avoid patient harm. RECENT FINDINGS: Recent prospective studies and studies of patient harm have advanced our understanding. Additionally, recent studies of fundus photography, telemedicine, and artificial intelligence highlight potential avenues for diagnostic improvement. Diagnostic error of neuro-ophthalmic conditions can often be traced to failure to gather an adequate history, perform a complete physical exam, obtain adequate/appropriate neuroimaging, and generate a complete, appropriate differential diagnosis. Improving triage and identification of neuro-ophthalmic conditions by other providers and increasing access to subspecialty neuro-ophthalmology evaluation are essential avenues to reduce diagnostic error. Further research should evaluate the relationship between misdiagnosis and patient harm, and help identify the most impactful potential targets for improvement.

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.

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.

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.

Diagnostic Error of Neuro-ophthalmologic Conditions: State of the Science.

BACKGROUND: Diagnostic error is prevalent and costly, occurring in up to 15% of US medical encounters and affecting up to 5% of the US population. One-third of malpractice payments are related to diagnostic error. A complex and specialized diagnostic process makes neuro-ophthalmologic conditions particularly vulnerable to diagnostic error. EVIDENCE ACQUISITION: English-language literature on diagnostic errors in neuro-ophthalmology and neurology was identified through electronic search of PubMed and Google Scholar and hand search. RESULTS: Studies investigating diagnostic error of neuro-ophthalmologic conditions have revealed misdiagnosis rates as high as 60%-70% before evaluation by a neuro-ophthalmology specialist, resulting in unnecessary tests and treatments. Correct performance and interpretation of the physical examination, appropriate ordering and interpretation of neuroimaging tests, and generation of a differential diagnosis were identified as pitfalls in the diagnostic process. Most studies did not directly assess patient harms or financial costs of diagnostic error. CONCLUSIONS: As an emerging field, diagnostic error in neuro-ophthalmology offers rich opportunities for further research and improvement of quality of care.

Referral Patterns in Neuro-Ophthalmology.

BACKGROUND: Neuro-ophthalmologists specialize in complex, urgent, vision- and life-threatening problems, diagnostic dilemmas, and management of complex work-ups. Access is currently limited by the relatively small number of neuro-ophthalmologists, and consequently, patients may be affected by incorrect or delayed diagnosis. The objective of this study is to analyze referral patterns to neuro-ophthalmologists, characterize rates of misdiagnoses and delayed diagnoses in patients ultimately referred, and delineate outcomes after neuro-ophthalmologic evaluation. METHODS: Retrospective chart review of 300 new patients seen over 45 randomly chosen days between June 2011 and June 2015 in one tertiary care neuro-ophthalmology clinic. Demographics, distance traveled, time between onset and neuro-ophthalmology consultation (NOC), time between appointment request and NOC, number and types of providers seen before referral, unnecessary tests before referral, referral diagnoses, final diagnoses, and impact of the NOC on outcome were collected. RESULTS: Patients traveled a median of 36.5 miles (interquartile range [IQR]: 20-85). Median time from symptom onset was 210 days (IQR: 70-1,100). Median time from referral to NOC was 34 days (IQR: 7-86), with peaks at one week (urgent requests) and 13 weeks (routine requests). Median number of previous providers seen was 2 (IQR: 2-4; range:0-10), and 102 patients (34%) had seen multiple providers within the same specialty before referral. Patients were most commonly referred for NOC by ophthalmologists (41% of referrals). Eighty-one percent (242/300) of referrals to neuro-ophthalmology were appropriate referrals. Of the 300 patients referred, 247 (82%) were complex or very complex; 119 (40%) were misdiagnosed; 147 (49%) were at least partially misdiagnosed; and 22 (7%) had unknown diagnoses. Women were more likely to be at least partially misdiagnosed-108 of 188 (57%) vs 39 of 112 (35%) of men (P < 0.001). Mismanagement or delay in care occurred in 85 (28%), unnecessary tests in 56 (19%), unnecessary consultations in 64 (22%), and imaging misinterpretation in 16 (5%). Neuro-ophthalmologists played a major role in directing treatment, such as preserving vision, preventing life-threatening complications, or avoiding harmful treatment in 62 (21%) patients. CONCLUSIONS: Most referrals to neuro-ophthalmologists are appropriate, but many are delayed. Misdiagnosis before referral is common. Neuro-ophthalmologists often prevent vision- and life-threatening complications.

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.

Diagnostic error and neuro-ophthalmology.

PURPOSE OF REVIEW: This review summarizes the recent literature on diagnostic error relevant to the practice of neuro-ophthalmology, and evaluates the potential for increased access to neuro-ophthalmology to decrease rates of diagnostic error, thereby reducing medical harm and spending on unnecessary tests and treatments. RECENT FINDINGS: Despite medical advances, current research continues to show alarmingly high rates of diagnostic error. Research into diagnostic error shows that many of these errors can be traced to cognitive errors. Recent studies on diagnostic problems relevant to neuro-ophthalmology, including studies of misdiagnosis of posterior communicating artery aneurysms, idiopathic intracranial hypertension, optic neuritis, and optic nerve sheath meningiomas, have identified major causes of diagnostic error in these conditions. SUMMARY: Studies on diagnostic error in neuro-ophthalmologic conditions show that prior to evaluation by a neuro-ophthalmologist, patients may undergo unnecessary tests and treatments that are costly and potentially harmful. Further research on diagnostic error will inform better utilization of neuro-ophthalmologists as a resource to decrease diagnostic error.

Steroid Treatment of Optic Neuropathies.

The etiologies of optic neuropathy include inflammation, ischemia, toxic and metabolic injury, genetic disease, and trauma. There is little controversy over the practice of using steroids in the treatment of optic neuritis--it is well established that intravenous steroid treatment can speed visual recovery but does not alter final visual function. However, there is controversy surrounding the acceptable routes of administration, dosage, and course of treatment. Additionally, the typical patient with optic neuritis is young and otherwise healthy, and thus is likely to tolerate steroids well. In ischemic and traumatic causes of optic neuropathies, the initial injury is not inflammatory, but damage may be compounded by secondary injury due to resultant inflammation and swelling in the confined space of the optic canal. Steroids have been considered as a means of minimizing inflammation and swelling, and thus minimizing the secondary injury that results. However, the use of steroids in traumatic and ischemic optic neuropathies is highly controversial-the evidence for the efficacy of treatment with steroids is insufficient to show that there is significant benefit. Additionally, patients with these conditions are more likely to have comorbidities that make them vulnerable to significant adverse events with the use of steroids. In this article, we attempt to analyze the current state of the literature regarding the use of steroids in the treatment of optic neuropathies, specifically optic neuritis, nonarteritic anterior ischemic optic neuropathy, and traumatic optic neuropathy.

Incidence and Causes of Overdiagnosis of Optic Neuritis.

Importance: Diagnostic error is an important source of medical error. Overdiagnosis of optic neuritis may prompt unnecessary and costly diagnostic tests, procedures, and treatments. Objective: To assess the incidence of and characterize factors contributing to overdiagnosis of acute optic neuritis. Design, Setting, and Participants: In this retrospective clinic-based cross-sectional study of new patient encounters, 122 patients referred for acute optic neuritis at a university-based Midwestern neuro-ophthalmology clinic between January 2014 and October 2016 were studied. Data were analyzed from September 2016 to July 2017. Interventions: Definite diagnosis was determined by neuro-ophthalmologists. For patients with alterative diagnoses, the Diagnosis Error Evaluation and Research taxonomy tool was applied to categorize the type of diagnostic error. Main Outcomes and Measures: The primary outcome was the primary type of diagnostic error in patients erroneously diagnosed as having optic neuritis. Secondary outcomes included final diagnosis and interventions undergone prior to referral. Results: A total of 122 patients were referred with acute optic neuritis during the study period; 88 (72.1%) were female, and the mean (SD) age was 42.6 (14.0) years. Of these, 49 patients (40.2%; 95% CI, 31.4-49.4) were confirmed to have optic neuritis, and 73 (59.8%; 95% CI, 50.6-68.6) had an alternative diagnosis. The most common alternative diagnoses were headache and eye pain, functional visual loss, and other optic neuropathies, particularly nonarteritic anterior ischemic optic neuropathy. The most common diagnostic error was eliciting or interpreting critical elements of history, which occurred in 24 of 73 patients (33%) with alternative diagnoses. Other common errors included errors weighing or considering alternative diagnoses (23 patients [32%]), errors weighing or interpreting physical examination findings (15 patients [21%]), and misinterpreting diagnostic test results (11 patients [15%]). In patients with alterative diagnoses, 12 (16%) had normal magnetic resonance imaging findings preceding the referral, 12 (16%) had received a lumbar puncture, and 8 (11%) had received unnecessary treatment with intravenous steroids. Conclusions and Relevance: These data suggest that nearly 60% (95% CI, 50.6-68.6) of patients referred for optic neuritis have an alternative diagnosis, with the most common errors being overreliance on a single item of history and failure to consider alternative diagnoses. Understanding pitfalls leading to overdiagnosis of optic neuritis may improve clinicians' diagnostic process.

More than the money: a review of the literature examining healthy volunteer motivations.

BACKGROUND AND OBJECTIVE: Few existing data report the motivations of healthy volunteers in clinical research trials. Some worry that volunteers consider only financial motivations. This study summarized and analyzed existing empirical research on self-reported motivations of healthy volunteers participating in studies not intended to offer benefit from participation. STUDY SELECTION: A systematic PubMed search was conducted. Inclusion criteria captured English-language empirical studies on the self-reported motivations, reasons, or factors influencing the decision of healthy volunteers to enroll in clinical research. Thirteen studies involving more than 2000 healthy volunteers met the criteria and were included in this review. DATA EXTRACTION: Independent review by the authors and extraction of information about the sample, methodology and objectives of the motivations study, description of the clinical trial and whether participation was actual or hypothetical, reported primary and secondary motivations of the healthy volunteers, risk evaluation, and reported differences in motivations related to sociodemographic variables. RESULTS: This review showed that although financial reward is the primary motivation for healthy volunteers to participate in clinical trials, financial motivations are one among many other reported motivations, including contributing to science or the health of others, accessing ancillary healthcare benefits, scientific interest or interest in the goals of the study, as well as meeting people and curiosity. Volunteers consider risk when making a decision about participation. CONCLUSIONS: Although financial incentives are important in recruiting healthy volunteers, their motivations are not limited to financial motivations. Further research is needed to examine motivations in different contexts and countries, the decision making of healthy volunteers, and the dynamics of repeat participation.