The Increasing Burden of Emergency Department and Inpatient Consultations for "Papilledema".

BACKGROUND: Increasing incidence of idiopathic intracranial hypertension (IIH), overreported radiologic signs of intracranial hypertension, difficult access to outpatient neuro-ophthalmology services, poor insurance coverage, and medicolegal concerns have lowered the threshold for emergency department (ED) visits for "papilledema." Our objective was to examine referral patterns and outcomes of neuro-ophthalmology ED and inpatient consultations for concern for papilledema. METHODS: At one university-based quaternary care center, all adults referred for "papilledema" over one year underwent a standardized ED "papilledema protocol." We collected patient demographics, final diagnoses, and referral patterns. RESULTS: Over 1 year, 153 consecutive patients were referred for concern for papilledema. After papilledema protocol, 89 of 153 patients (58%) had bilateral optic disc edema, among whom 89% (79/89) had papilledema (intracranial hypertension). Of the 38 of 153 (25%) consultations for suspected disorder of intracranial pressure without previous fundus examination (Group 1), 74% (28/38) did not have optic disc edema, 21% (8/38) had papilledema, and 5% (2/38) had other causes of bilateral disc edema. Of the 89 of 153 (58%) consultations for presumed papilledema seen on fundus examination (Group 2), 58% (66/89) had confirmed papilledema, 17% (15/89) had pseudopapilledema, and 9% (8/89) had other causes of bilateral optic disc edema. Of the 26 of 153 (17%) patients with known IIH (Group 3), 5 had papilledema and 4 required urgent intervention. The most common diagnosis was IIH (58/79). Compared with IIH, patients with secondary causes of intracranial hypertension were older (P = 0.002), men (P < 0.001), not obese (P < 0.001), and more likely to have neurologic symptoms (P = 0.002). CONCLUSION: Inpatient and ED consultations for "papilledema" are increasing. Of the 153 ED and inpatient neuro-ophthalmology consultations seen for "papilledema" over 1 year, one-third of patients with optic disc edema of unknown cause before presentation to our ED had new vision- or life-threatening disease, supporting the need for prompt identification and evaluation of optic disc edema in the ED. In the face of limited access to neuro-ophthalmologists, this study supports the need for emergency department access to expert eye-care evaluation or ocular fundus camera for prompt identification of optic disc edema and standardized evaluation for neurologic emergencies.

Nonneurologic causes of binocular diplopia for the neurologist.

PURPOSE OF REVIEW: To review several etiologies of nonneurologic diplopia that the neurologist should be familiar with. The pathophysiology, clinical presentation, neuroimaging findings, and treatment options are briefly summarized for each condition. RECENT FINDINGS: Certain etiologies for diplopia can be associated with life-threatening neurologic conditions and should be investigated thoroughly for proper localization and immediate management of the underlying disease. However, nonneurological causes of binocular diplopia are very common and disabling, but are often nonemergent and may not require in-depth investigation or neuroimaging. Some of the etiologies of nonneurologic diplopia mimic cranial nerve palsies, making them confusing to evaluate when the physician is not familiar with these etiologies. Unfamiliarity with these diagnoses can lead to unnecessary neuroimaging, inefficient utilization of medical resources, and undue alarm to the patient. Recent advances in clinical diagnostic tools and neuroimaging have clarified our understanding of the diverse underlying mechanisms of nonneurologic binocular diplopia. SUMMARY: Diplopia can be a difficult symptom for the neurologist to evaluate. A systematic approach to the evaluation of diplopia can help establish the urgency and necessity of an extensive workup.This review will help to familiarize the neurologist with nonneurological causes of binocular diplopia, minimize expensive and unnecessary evaluations, and reassure patients and physicians alike.

Neuro-ophthalmology Emergency Department and Inpatient Consultations at a Large Academic Referral Center.

PURPOSE: Prompt neuro-ophthalmology consultation prevents diagnostic errors and improves patient outcomes. The scarcity of neuro-ophthalmologists means that the increasing outpatient demand cannot be met, prompting many emergency department (ED) referrals by non-neuro-ophthalmologists. We describe our quaternary care institution's ED and inpatient neuro-ophthalmology consultation patterns and patient outcomes. DESIGN: Prospective observational study. PARTICIPANTS: Consecutive neuro-ophthalmology ED and inpatient consultation requests over 1 year. METHODS: We collected patient demographics, distance traveled, insurance status, referring provider details, consultation question, final diagnosis, complexity of consultation, time of consultation, and need for outpatient follow-up. MAIN OUTCOME MEASURES: Consultation patterns and diagnoses, complexity, and follow-up. RESULTS: Of 494 consecutive adult ED and inpatient neuro-ophthalmology consultations requested over 1 year, 241 of 494 consultations (49%) occurred at night or during weekends. Of ED consultations (322 of 494 [65%]), 127 of 322 consultations (39%) occurred during weekdays, 126 of 322 consultations (39%) occurred on weeknights, and 69 of 322 consultations (22%) occurred on weekends or holidays. Of 322 ED consultations, 225 of 322 consultations (70%) were patients who initially sought treatment in the ED with a neuro-ophthalmic chief symptom. Of the 196 patients sent to the ED by a health care professional, 148 patients (148/196 [76%]) were referred by eye care specialists (74 optometrists and 74 ophthalmologists). The most common ED referral questions were for papilledema (75 of 322 [23%]) and vision loss (72 of 322 [22%]). A total of 219 of 322 patients (68%) received a final active neuro-ophthalmic diagnosis, 222 of 322 patients (69%) were cases of high or very high complexity, and 143 of 322 patients (44%) required admission. Inpatient consultations (n = 172) were requested most frequently by hospitalists, including neurologists (71 of 172 [41%]) and oncologists (20 of 172 [12%]) for vision loss (43 of 172 [25%]) and eye movement disorders (36 of 172 [21%]) and by neurosurgeons (58 of 172 [33%]) for examination for mass or a preoperative evaluation (19 of 172 [11%]). An active neuro-ophthalmic diagnosis was confirmed in 67% of patients (116 of 172). Outpatient neuro-ophthalmology follow-up was required for 291 of 494 patients (59%). CONCLUSIONS: Neuro-ophthalmology consultations are critical to the diagnosis and management in the hospital setting. In the face of a critical shortage of neuro-ophthalmologists, this study highlights the need for technological and diagnostic aids for greater outpatient access. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visual outcomes after bevacizumab-based therapy for optic pathway glioma.

In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This single-institution study characterized visual acuity (VA) and visual field (VF) outcomes in 17 pediatric OPG patients treated with BBT. VA was stable or improved in 14 patients. Nine patients had evaluable VF data, six of whom experienced stability or improvement. Among six patients with vision deterioration as a treatment indication, stable or improved was observed for both VA and VF in five patients. In summary, BBT was associated with favorable visual outcomes in this cohort of patients with OPG.

Vision-related quality-of-life in pediatric primary brain tumor patients.

PURPOSE: Brain tumors are the leading cause of death from childhood cancer. Although overall survival has improved due to earlier detection, better therapies, and improved surveillance, visual dysfunction and impaired vision-related quality-of-life (VR-QOL) are often unrecognized in children. This project investigated VR-QOL in pediatric brain tumor patients. METHODS: We evaluated visual impairment and quality-of-life (QOL) in a quality improvement project at one tertiary care center. Patients ≤ 18, greater than 6 months from diagnosis of brain tumor, excluding intrinsic anterior visual pathway tumors, underwent standardized neuro-ophthalmologic examination. Health-related QOL (HR-QOL) (PedsQL Brain Tumor Module) and VR-QOL questionnaires [CVFQ (Children's Visual Function Questionnaire) in children < 8, and EYE-Q in children 8-18] were obtained from patients and parents. RESULTS: Among 77 patients, craniopharyngiomas (n = 16, 21%) and astrocytomas (n = 15, 20%) were the most common tumors. Among 44/77 (57%) visually impaired children, 7 (16%) were legally blind. Eye-Q median score was 3.40 (interquartile range 3.00-3.75), worse than average scores for normal children. Eye-Q score decreased 0.12 with every 0.1 increase in logMAR visual acuity (p < 0.001). Patients who were legally blind had a significantly lower Eye-Q score than those who were not [0.70 vs. 3.44 (p < 0.001)]. Cognitive HR-QOL scores decreased 1.3 for every 0.1 increase in logMAR visual acuity (p = 0.02). CONCLUSIONS: Pediatric brain tumor patients' vision, HR-QOL, and VR-QOL were often severely affected even when tumors were considered cured. Visual acuity and legal blindness correlated with VR-QOL. Systematic neuro-ophthalmologic examinations in pediatric primary brain tumor patients are necessary to facilitate early preventative and corrective ophthalmologic interventions.

Unilateral Isolated Paucisymptomatic Optic Disc Edema.

BACKGROUND: Unilateral isolated optic disc edema (UIODE) represents a challenging clinical presentation that frequently precipitates an extensive diagnostic work-up. Patients without an apparent diagnosis despite appropriate investigations are often categorized as having "papillophlebitis," an entity that is poorly defined in the existing literature. Our aim was to describe the characteristics of a series of patients with paucisymptomatic UIODE, determine the optimal diagnostic approach to such cases, and clarify the clinical features of presumed papillophlebitis. METHODS: We retrospectively identified 29 patients with UIODE who were seen by neuro-ophthalmologists at a single center between 2005 and 2019. Each patient presented with isolated, unilateral disc edema that was either entirely asymptomatic or associated with minimal visual symptoms. Patients underwent a comprehensive neuro-ophthalmic evaluation and several ophthalmic and systemic investigations. Data from the initial visit and all subsequent clinical visits were collected, including patient demographics, examination findings, and details of the diagnostic work-up. RESULTS: Our 29 patients with UIODE were found to have a variety of underlying diagnoses including unilateral papilledema due to idiopathic intracranial hypertension (10 patients), optic nerve sheath meningioma (5), incipient nonarteritic anterior ischemic neuropathy (4), vitreopapillary traction (3), orbital masses (2), a peripapillary choroidal neovascular membrane (1), and presumed papillophlebitis (4). The duration of disc edema varied considerably based on the etiology, but most patients had favorable visual outcomes. CONCLUSIONS: A systematic approach to the evaluation of UIODE, combined with long-term follow-up, led to a definite diagnosis in a majority of patients, with only 4 patients presumed to have papillophlebitis, a diagnosis the actual existence of which remains controversial.

Very Poor Visual Acuity in Non-Arteritic Anterior Ischaemic Optic Neuropathy.

Very poor (hand motion or worse) visual acuity at presentation is highly unusual in non-arteritic anterior ischaemic optic neuropathy. We retrospectively reviewed the medical records of 151 consecutive non-arteritic anterior ischaemic optic neuropathy patients seen at our institution between July 2014 and April 2016 to evaluate the frequency and characteristics of patients with very poor visual acuity in non-arteritic anterior ischaemic optic neuropathy. Hand motion or worse visual acuity was documented in 17 patients (11%); all patients had at least one vascular risk factor and 14 (82%) had at least two vascular risk factors. Although severe vision loss at presentation does occur in non-arteritic anterior ischaemic optic neuropathy, an extensive workup should be obtained to rule out another cause, especially arteritic anterior ischaemic optic neuropathy.

Influence of Optic Nerve Appearance on Visual Outcome in Pediatric Idiopathic Intracranial Hypertension.

OBJECTIVES: To determine whether optic disc hemorrhages (ODH) and cotton wool spots (CWS) at presentation are associated with worse visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH). METHODS: Retrospective institutional review of 100 eyes of 50 consecutive pediatric IIH patients (aged 16 years or less) who had baseline optic disc photographs before or within 30 days of their diagnostic lumbar puncture and initiation of medical treatment. Optic disc photographs were independently graded by three ophthalmologists in a standardized manner. Visual function was assessed using visual acuity (VA) and visual field grade (VFG). RESULTS: At least one ODH was found in 41% of eyes, at least one CWS was found in 27% of eyes, and 20% of eyes had both ODH and CWS. At presentation, Frisén grade was associated with the presence of CWS (p = 0.013) and showed no association with ODH (p = 0.060). When controlling for Frisén grade, ODH and CWS were not associated with worse VA or VFG at final follow-up. Severe ODH were associated with worse VA and VFG at presentation (p < 0.03), but not at final follow-up. Severe CWS at presentation was strongly associated with a worse Humphrey mean deviation of 5.0 dB (95% confidence interval 1.6-8.3) at final follow-up (p = 0.002). CONCLUSION: When controlling for the severity of papilledema, ODH do not provide any additional prognostic value in pediatric IIH patients. Frisén grade and severe CWS at presentation were independently associated with worse visual outcomes at the final follow-up.

Very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor.

Involvement of the pituitary gland by leukemic infiltration is exceedingly rare. Here, we describe a very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor and review the literature for previously reported cases. Our female patient presented 13 years after completion of therapy for B-ALL with headache, amenorrhea, galactorrhea and a pituitary mass. Subsequent studies revealed recurrence of her leukemia, and the pituitary lesion resolved after induction chemotherapy. Our case highlights the importance of considering leukemic infiltrate in the differential diagnosis of pituitary mass, particularly in a patient with a history of hematologic malignancy, sparing unnecessary surgical intervention and informing endocrine evaluation. In addition, the case also highlights difficulties with characterizing this recurrence as a very late relapse or clonal evolution of the original leukemia.

Multirater Validation of Peripapillary Hyperreflective Ovoid Mass-like Structures (PHOMS).

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a new retinal optical coherence tomography (OCT) finding. The Optic Disc Drusen Studies Consortium had made recommendations to distinguish PHOMS from true optic disc drusen (ODD) in 2018. While publications on PHOMS have increased since then, the accuracy of the definition of PHOMS and reliability of detection is unknown. In this multi-rater study, we demonstrate that the 2018 definition of PHOMS resulted in a poor multi-rater kappa of 0.356. We performed a Delphi consensus process to develop a consistent and refined definition of PHOMS with clear principles around the nature of PHOMS and how they differ from normal anatomy. Fifty explanatory teaching slides, provided as supplementary material, allowed our expert group of raters to achieve a good level of agreement (kappa 0.701, 50 OCT scans, 21 raters). We recommend adopting the refined definition for PHOMS.

Visual function in children with primary brain tumors.

PURPOSE OF REVIEW: To review the recent advances in understanding how primary brain tumors affect vision in children. RECENT FINDINGS: Children with primary brain tumors may have vision loss due to involvement of their afferent visual pathways or from papilledema. These vision deficits may go unrecognized until later in life, years after treatment of the primary lesion. Strabismus and cranial nerve palsies may occur as a result of brain tumors. Ophthalmologists can monitor and treat young children at risk for vision loss from amblyopia as a result of effects from their underlying lesion. Advances in imaging techniques have made it possible to quantify damage to the visual pathways with objective tests. SUMMARY: Systematic referrals for evaluation by an ophthalmologist should occur early in the course of treatment of primary brain tumors as these evaluations may improve visual outcomes and quality of life.

Update on pediatric optic neuritis.

PURPOSE OF REVIEW: To summarize recent developments in the classification, investigation and management of pediatric optic neuritis (PON). RECENT FINDINGS: A recent surge in interest surrounding antibodies to myelin oligodendrocyte glycoprotein antibody (MOG-Ab) has instigated a paradigm shift in our assessment of children with PON. This serological marker is associated with a broad spectrum of demyelinating syndromes that are clinically and radiologically distinct from multiple sclerosis (MS) and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). Optic neuritis is the most common presenting phenotype of MOG-Ab positive-associated disease (MOG+AD). MOG-Ab seropositivity is much more common in the pediatric population and it predicts a better prognosis than MS or AQP4+NMOSD, except in the subset that exhibit a recurrent phenotype. SUMMARY: A better grasp of MOG+AD features and its natural history has facilitated more accurate risk stratification of children after a presenting episode of PON. Consequently, the initial investigation of PON has broadened to include serology, along with neuroimaging and cerebrospinal fluid analysis. Acute treatment of PON and chronic immunotherapy is also becoming better tailored to the suspected or confirmed diagnoses of MS, AQP4+NMOSD and MOG+AD.

Lack of Relationship between Central Corneal Thickness and Papilloedema in Idiopathic Intracranial Hypertension.

Translaminar pressure gradient abnormalities have been implicated in the pathogenesis and progression of glaucoma. A "reversed" translaminar pressure gradient may be related to papilloedema severity in idiopathic intracranial hypertension. Central corneal thickness is related to intraocular pressure measurements and, by extension, to translaminar pressure gradients. We evaluated if central corneal thickness could be a marker of worse papilloedema due to altered translaminar pressure gradients in patients with idiopathic intracranial hypertension. We found that central corneal thickness was not related to the severity of papilloedema in idiopathic intracranial hypertension.

Pitfalls in the Use of Stereoacuity in the Diagnosis of Nonorganic Visual Loss.

PURPOSE: The Titmus Stereotest (Stereo Optical Co., Inc., Chicago, IL) has been used to estimate visual acuity (VA) in the evaluation of nonorganic visual loss. Previous predictions were derived from optical degradation of VA in normal subjects and may not account for the variability seen in patients with neuro-ophthalmic pathologies included in the differential diagnosis of nonorganic visual loss. The purpose of this study was to evaluate the relationship between Titmus stereoacuity and minimal VA based on a real-world testing environment. DESIGN: Cross-sectional observational study. PARTICIPANTS: All patients treated at the authors' neuro-ophthalmology service between April 25, 2014, and July 31, 2014. METHODS: All subjects underwent routine neuro-ophthalmic examination, including Titmus stereoacuity measurements. A compound Bayesian logit-lognormal model accounting for heteroscedasticity was used to determine 95% and 99% prediction intervals of the worse eye's near VA based on stereoacuity. Logarithm of the minimum angle of resolution VA and log stereoacuity were analyzed. MAIN OUTCOME MEASURES: Titmus stereoacuity and worse eye VA. RESULTS: Of 561 patients, 364 subjects 11 to 91 years of age were included. Titmus stereoacuity was associated positively with VA: 9 circles correct (40 seconds of arc) indicated VA of at least 20/40 with 95% confidence and VA of at least 20/79 with 99% confidence; 6 circles correct (80 seconds of arc) indicated VA of at least 20/62 and 20/180, respectively; and 4 circles correct (140 seconds of arc) indicated VA of at least 20/110 and 20/570, respectively. CONCLUSIONS: When fully accounting for individual variation and the full spectrum of neuro-ophthalmic diseases affecting VA, stereoacuity remains associated with VA, but previous commonly used VA estimates based on stereoacuity overestimated VA. Our results more accurately predict minimum VA from Titmus stereoacuity and should be used preferentially when evaluating patients with suspected nonorganic visual loss. We demonstrated that Titmus stereoacuity cannot definitively establish normal VA, and therefore can suggest, but not fully establish, the diagnosis of nonorganic visual loss.

Diplopia-An Update.

Diagnosing the underlying etiology of diplopia requires a structured approach. Double vision can arise from ocular, mechanical, or neurologic causes. A careful history can greatly improve a targeted examination. The approach to initial diagnosis and examination in cases of diplopia has been previously described. Here the authors expand upon those recommendations, and add new techniques recently described in the literature, which may influence the approach to the diplopia patient. A description of the approach to the examination of torsion is discussed. The "three-step test" in the diagnosis of vertical strabismus is discussed, and recent advances in diagnosing skew deviation with the upright-supine test are described. Mechanical strabismus due to changes in orbital anatomy is also reviewed. This review should help the reader refine the differential diagnosis of the patient with diplopia.

Relationship Between Age, Gender, and Race in Patients Presenting With Myasthenia Gravis With Only Ocular Manifestations.

BACKGROUND: The demographic associations among patients presenting with myasthenia gravis with only ocular manifestations (OMG) is not clear. METHODS: In this 5-center case series, we collected the race, gender, and age at diagnosis of patients diagnosed with myasthenia gravis who had no signs or symptoms of generalized myasthenia gravis (GMG). An a priori sample size calculation determined that 140 patients were required to accept that there was a ≤10-year difference in mean age (equivalence testing: power 90%, α = 0.05). Robust Bayesian analysis and linear regression were applied to evaluate whether age differed by gender or race. RESULTS: Of 433 patients included, 258 (60%) were men. Mean age among men was 57 years (SD = 19) and 52 years (SD = 21) among women. The 95% credible interval (CI) (Bayesian equivalent of confidence interval) was 0.8-8.7 years for mean age, and there was a 99.6% probability that the mean difference in age between sexes was <10 years. Race was documented in 376 (68 [18%] non-Caucasian). Caucasians were 17.3 years older than non-Caucasians at diagnosis (95% CI, 12.2-22.3 y; P < 0.001) controlling for gender. There was no additive interaction of gender and race (P = 0.74). There was a bimodal distribution for women peaking around 30 and 60 years. Men had a left skewed unimodal age distribution peaking at age 70. CONCLUSIONS: The distribution of age at presentation in patients with OMG is different between men and women, similar to GMG. Non-Caucasian patients tend to develop OMG at a younger age.

The Effects of Primary Brain Tumors on Vision and Quality of Life in Pediatric Patients.

Brain tumors are the leading cause of death from childhood cancer. Overall survival has improved due to earlier detection, better therapies, and improved posttreatment surveillance. Permanent sequelae of the tumor and its treatment may cause severe impairment and decreased quality of life (QoL). Pediatric primary brain tumor patients' vision can be severely affected, even when the tumor location does not primarily involve the visual pathway. Visual dysfunction and impaired vision-related QoL may not be detected or screened for in children with primary brain tumors for many reasons, including examination difficulty and lack of awareness. The authors review the ophthalmic presenting symptoms, effects on vision, and quality of life in pediatric patients with primary brain tumors. They also describe and emphasize the importance of systematic neuro-ophthalmologic examinations in this population, which may improve long-term visual and QoL outcomes through earlier interventions.

Is there treatment for Leber hereditary optic neuropathy?

PURPOSE OF REVIEW: To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome. RECENT FINDINGS: Idebenone has been proposed as a means of bypassing defective complex I activity and a free radical scavenger to prevent oxidative damage. EPI-743 may have more potency than idebenone, but no clinical trials have been performed. Gene therapy techniques have advanced significantly, including allotopic expression and nuclear transfer. Successful rescue of animal models of LHON with both of these therapies has been demonstrated. Introduction of exogenous DNA into the mitochondrial genome with mitochondrial targeting of viral vectors is another promising technique. SUMMARY: There are currently no proven treatments for LHON. However, there are many promising novel treatment modalities that are currently being evaluated, with several clinical trials underway or in the planning stages. Supportive measures and genetic counseling remain of great importance for these patients.