J Neuroophthalmol
· 2025 Dec · PMID 40378038
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BACKGROUND: Serial fundus photography is commonly used to differentiate between papilledema and pseudopapilledema, but there are limited data on the interrater reliability and accuracy of interpreting these images in chi...BACKGROUND: Serial fundus photography is commonly used to differentiate between papilledema and pseudopapilledema, but there are limited data on the interrater reliability and accuracy of interpreting these images in children. The purpose of this study was to evaluate the agreement and accuracy of pediatric neuro-ophthalmologists in classifying fundus photographs of children with papilledema and pseudopapilledema. METHODS: For this cross-sectional study, 3 masked experts (pediatric neuro-ophthalmologists) classified a multicenter image collection from children with a clinical diagnosis of either papilledema or pseudopapilledema, which was determined based on the results of history, examination, ancillary ophthalmic imaging, neuroimaging, and/or lumbar puncture. Fleiss kappa (κ) was calculated to assess interrater agreement; accuracy, sensitivity, and specificity were calculated to determine expert performance. Subgroup analyses according to papilledema grade and expert certainty were performed. RESULTS: Six hundred fifty-nine photographs from 171 children were included. The full data set, papilledema, and pseudopapilledema κ values were 0.36 (0.32-0.42), 0.40 (0.32-0.49), and 0.28 (0.22-0.34), respectively. Accuracy, sensitivity, and specificity ranged from 58.9% to 63.9%, 54.3% to 76.0%, and 56.1% to 62.6%, respectively, among the 3 experts. Grade 1 papilledema was associated with inaccurate agreement (misinterpretation as pseudopapilledema by all 3 experts) in 31.8% and disagreement in 59.0% of cases. Higher grades of papilledema were associated with higher rates of accurate agreement. All experts achieved high sensitivity in classifying photographs of moderate-to-high-grade papilledema (85%-94%). CONCLUSIONS: Overall agreement was low among pediatric neuro-ophthalmologists when classifying fundus photographs of children with papilledema and pseudopapilledema. When interpreting low-grade papilledema images, inaccurate agreement and disagreement were more likely than accurate agreement among experts. Our study highlights the limitations of interpreting fundus photographs of children with papilledema and pseudopapilledema in isolation, stressing the importance of obtaining a complete neuro-ophthalmologic history and examination, as well as other ancillary ophthalmic imaging, to guide decision making regarding systemic workup.
BACKGROUND: This study explored ischemic stroke occurrence in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and assess the link between NAION and carotid artery stenosis (CAS) as an ischemic strok...BACKGROUND: This study explored ischemic stroke occurrence in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and assess the link between NAION and carotid artery stenosis (CAS) as an ischemic stroke risk factor. METHODS: A retrospective (2009-2019) nationwide, population-based study was conducted using a cohort database from Clalit, the largest healthcare network in Israel. Among 1,200,000 insured individuals, 605 NAION patients without prior ischemic stroke diagnosis were included, matched with a 10-fold larger comparison group by age, sex, and cardiovascular risk factors. RESULTS: Results indicated a higher incidence of large-vessel ischemic stroke (18.7% vs 14.7% in the comparison group) and small-vessel ischemic stroke (4.8% vs 3.1% in the comparison group) in patients with NAION. CAS prevalence was elevated in patients with NAION both during the study and during follow-up. Multivariable analysis showed hazard ratios of 1.5 ( P = 0.002) for large-vessel ischemic strokes and 1.56 ( P = 0.031) for small-vessel ischemic strokes in patients with NAION. The cumulative probability of ischemic strokes for patients with NAION without risk factors was higher than for the comparison group without risk factors (log rank test, P = 0.017). CONCLUSIONS: These population-based study results revealed a higher incidence of ischemic stroke after a NAION episode compared with the comparison group. This association was valid regardless of any additional vascular risk factors. There is a need to consider specific management for patients with NAION diagnosed with carotid artery stenosis because of the potential for a triadic relationship among the 3 conditions.
BACKGROUND: Godtfredsen syndrome (GS), originally described by Dr. Erik Godtfredsen in 1946, is the combination of cranial nerve (CN) 6th and 12th palsies. The most common etiology of GS is a lesion of the clivus. METHOD...BACKGROUND: Godtfredsen syndrome (GS), originally described by Dr. Erik Godtfredsen in 1946, is the combination of cranial nerve (CN) 6th and 12th palsies. The most common etiology of GS is a lesion of the clivus. METHODS: A retrospective case series of GS is described. RESULTS: Three patients were included: 1) a 38-year-old woman with a clival breast cancer metastasis; 2) a 35-year-old woman with a clival chordoma; and 3) a 72-year-old woman with a partially embolized dural arteriovenous fistula involving the hypoglossal canal. CONCLUSIONS: GS is a combination of CN 6th and 12th palsies and most commonly is due to a lesion in the clivus. Clinicians should be aware of this uncommon combination of cranial nerve findings, the localizing significance, and the differential diagnosis of clival lesions.
Shaia JK, Alam TA, Trinh IP
… +6 more, Rock JR, Chu JY, Schiltz NK, Singh RP, Talcott KE, Cohen DA
J Neuroophthalmol
· 2025 Dec · PMID 40369727
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BACKGROUND: Idiopathic intracranial hypertension (IIH) is a vision-threatening disorder mainly affecting women of a reproductive age. Prompt diagnosis and intervention are vital to prevent vision loss, but validated tool...BACKGROUND: Idiopathic intracranial hypertension (IIH) is a vision-threatening disorder mainly affecting women of a reproductive age. Prompt diagnosis and intervention are vital to prevent vision loss, but validated tools to predict visual outcomes are lacking. The purpose of this study was to create a machine learning algorithm predicting poor visual outcomes at the time that the diagnosis of IIH is established, and stratifying risk among those with and without poor visual acuity at presentation. METHODS: Using electronic health records, a retrospective cohort study was conducted between June 1, 2012 and September 30, 2023. Any patient aged 0-70 years who was diagnosed with IIH and met the revised diagnostic criteria was included in the analysis. In total, 391 patients with IIH had final outcomes available and were included in this analysis. Final visual outcomes were reported between 3 months and 1 year after diagnosis. Poor visual outcomes served as the model outcome and was defined as a visual field mean deviation (VFMD) worse than -7 dB or a visual acuity of 20/80 or worse. Both logistic regression and decision trees were used to build predictive models. Models were evaluated using multiple parameters including accuracy, sensitivity, specificity, and area under the curve. The best performing models were validated using a k-fold cross-validation. RESULTS: The decision tree models performed the best and 4 prognostic risk groups were created: critical, high, medium, and low. In the critical risk group, patients who had both high baseline VFMD (worse than -12.59 dB) and identified as non-White had a poor visual outcome risk of 92.6%. A baseline VFMD worse than -9.1 dB resulted in a critical risk of a poor visual outcome at 69.8%. Any patient with a baseline VFMD better than -3.39 dB had a risk of a poor visual outcome at 1.04%. CONCLUSIONS: Our study provides clinicians with valuable prognostic markers to assist in identifying patients who are at critical risk for significant vision loss. Patients with a VFMD worse than -9.1 dB have a critical risk of a poor visual outcome, and this further increased if they identified as a minority patient.
BACKGROUND: This study describes the clinical presentation, diagnostic yield, and outcomes of patients who have undergone optic nerve or nerve sheath biopsies. METHODS: A total of 72 patients undergoing an optic nerve or...BACKGROUND: This study describes the clinical presentation, diagnostic yield, and outcomes of patients who have undergone optic nerve or nerve sheath biopsies. METHODS: A total of 72 patients undergoing an optic nerve or optic nerve sheath biopsy at Mayo Clinic, Rochester, MN; Jacksonville, FL; or Scottsdale, AZ were included. Patients were identified by searching the pathology database between January 1, 2000, and December 31, 2023. Charts were reviewed to confirm the site of biopsy and review the patient's presentation, clinical course, and indication for biopsy. The main outcome measure was the diagnostic yield. RESULTS: Of the 72 patients included, 32 underwent optic nerve and 40 optic nerve sheath biopsies. The median age at biopsy was 34 years (range, 1-81 years), and 44 patients (61%) were female. The median preoperative visual acuity was no light perception (NLP) (range, 20/20 to NLP). Prebiopsy optic disc appearance was pallor in 32 (44%), edema in 18 (25%), normal in 11 (15%), and edema with pallor in 5 (7%) patients. Surgical approach was by orbitotomy in 43 (60%), craniotomy in 25 (35%), and trans-nasal in 4 (5%) patients. A definitive diagnosis was achieved on 48 biopsies of 72 patients with an unexplained optic neuropathy, thus giving a diagnostic yield of 67%, higher in optic nerve biopsies (81%) compared with nerve sheath biopsies (55%). The most common diagnoses were meningioma in 23 (32%), glioma in 9 (13%), and sarcoidosis in 6 (8%) patients. For all patients, postbiopsy complications occurred in 11 patients (18%), including strabismus in 5 (7%) patients and acute unexpected vision loss in 4 (6%) patients. The patients in this cohort were followed for a median of 3.3 years, and visual acuity at most recent visit was NLP (range, 20/20 to NLP). CONCLUSIONS: Based on our study, the diagnostic yield of optic nerve and optic nerve sheath biopsies was 67%. The potential diagnostic benefits of an optic nerve and optic nerve sheath biopsies may be offset by the possible permanent postsurgical complications.
BACKGROUND: Patients with idiopathic intracranial hypertension (IIH) have reported being told to discontinue their hormonal contraceptive, despite a lack of evidence in the literature. We aimed to determine the frequency...BACKGROUND: Patients with idiopathic intracranial hypertension (IIH) have reported being told to discontinue their hormonal contraceptive, despite a lack of evidence in the literature. We aimed to determine the frequency of this counseling and explore the content of discussion that other providers gave to patients with idiopathic intracranial hypertension regarding their use of hormonal contraception before neuro-ophthalmic assessment. METHODS: A survey of female subjects, aged 18-50 years, who had been advised or counseled regarding idiopathic intracranial hypertension and hormonal contraception. They were asked additional questions depending on their responses. RESULTS: Attempted contact of 230 subjects resulted in a response rate of 37% for a total of 85 respondents. Twenty four subjects declined participation. The total number of subjects surveyed was 61. Nearly half of all surveyed subjects reported taking a form of contraception at the time of their idiopathic intracranial hypertension diagnosis. Nearly 1 in 4 subjects reported being counseled regarding idiopathic intracranial hypertension and contraception. One in 10 of subjects who reported taking a contraceptive at the time of their diagnosis recalled a recommendation to cease their contraceptive recommendation before seeing a neuro-ophthalmologist. CONCLUSIONS: Nearly 10% of patients with idiopathic intracranial hypertension in our study who were taking contraception were inappropriately counseled to cease their use before neuro-ophthalmic referral. Ophthalmologists and neuro-ophthalmologists can help further benefit their patients by providing proactive education illustrating the lack of convincing evidence establishing a causal relationship between hormonal contraceptives and idiopathic intracranial hypertension.
BACKGROUND: Before 1895, all anatomic, pathologic, and functional understanding of the visual system was provided by postmortem studies. The advent of neuroimaging in 1895 with the development of X-ray technology enabled...BACKGROUND: Before 1895, all anatomic, pathologic, and functional understanding of the visual system was provided by postmortem studies. The advent of neuroimaging in 1895 with the development of X-ray technology enabled the living brain to be visualized, including the intraorbital and intracranial visual pathways. This has been augmented with the development of computed tomography, magnetic resonance imaging, and positron emission tomography. EVIDENCE ACQUISITION: A literature review of the history of neuroimaging of the visual axis was completed from the time of antiquity to the present day. RESULTS: The ability to visualize intracranial and orbital anatomy has been completely transformed. Imaging the visual axis has become faster, easier, and more precise allowing earlier diagnosis and management of a multitude of neuro-ophthalmic conditions. As we look to the future of neuroimaging, there is momentum to improve techniques enabling the assessment of microstructural architecture, metabolic and functional changes, and genetic biomarkers of disease. CONCLUSIONS: The development of high-resolution, multiplanar neuroimaging revolutionized the ability to visualize neuro-ophthalmic anatomy and pathology. Continued research will expand our ability to integrate the metabolic, anatomic, and connectivity profiles of the visual system.
BACKGROUND: A video-based assessment of the light-induced eyelid reflex, termed the photic blink reflex (PBR), was quantified based on the degree of palpebral fissure (PF) narrowing as a noninvasive test of visual input....BACKGROUND: A video-based assessment of the light-induced eyelid reflex, termed the photic blink reflex (PBR), was quantified based on the degree of palpebral fissure (PF) narrowing as a noninvasive test of visual input. The physiology of PF narrowing in response to light intensity was compared to the pupil light reflex, measured simultaneously. METHODS: Eyelid and pupil responses to flashes of white light stimulus, increasing in intensity, were video recorded in 53 subjects using a monocular hand-held device. Responses to photopic red and blue light stimuli were recorded in 5 subjects. Percent-change of PF width and pupil width from the prestimulus baseline was measured. RESULTS: In 81% of subjects, there was significant correlation between PF narrowing and light stimulus intensity. There was no correlation between the PBR and the pupil light reflex in the same eye in normal subjects. There was no sustained postillumination PF narrowing to bright blue-light stimuli compared to the postillumination sustained pupil response that was present in response to the same stimulus. CONCLUSIONS: The photic blink reflex can be quantified with video recording of the palpebral fissure. The photic blink reflex has potential utility as an alternative to the pupil light reflex in assessing asymmetric pathologies of the afferent visual pathway, especially in eyes with pharmacologically dilated or unreactive pupils.
Handzic A, Furter MP, Messmer BC
… +5 more, Wirth MA, Valko Y, Fierz FC, Margolin EA, Weber KP
J Neuroophthalmol
· 2026 Mar · PMID 40257852
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BACKGROUND: Diagnosing ocular myasthenia gravis (OMG) remains challenging despite recent diagnostic advances. We addressed this challenge by developing and validating a multivariable prediction model that estimates the O...BACKGROUND: Diagnosing ocular myasthenia gravis (OMG) remains challenging despite recent diagnostic advances. We addressed this challenge by developing and validating a multivariable prediction model that estimates the OMG probability given the results of any partial selection of available diagnostic tests. METHODS: The source data for our model were retrieved from our blinded prospective diagnostic accuracy study at the University Hospital Zurich (USZ). Patients with ptosis and/or diplopia whose presentation was suspicious for OMG underwent comprehensive diagnostic testing. An independent neuromuscular specialist made the final diagnosis. These data were used to fit and validate a Bayesian network model against additional retrospective USZ and the University of Toronto (UoT) patient data. The primary outcome was to predict the likelihood of a positive OMG diagnosis given the available diagnostic tests. For any set of tests, the model returns an OMG probability together with 95% credible intervals, indicating the prediction uncertainty. RESULTS: Of 89 patients included in the development of the model, 39 were diagnosed with OMG. Based on our Bayesian network model, the following variables were the most useful predictors in descending order: edrophonium test, acetylcholine receptor (AChR) antibodies), single-fiber electromyogram (sfEMG), repetitive nerve stimulations (RNS) facial nerve, RNS accessory nerve, Besinger score, ice test, sustained upgaze test, dysarthria, dyspnea, dysphagia, diplopia, ptosis, age, and sex. The model was validated by determining the mean error rate and the area under the curve (AUC) by both 10-fold cross-validation and prediction on the retrospective USZ and UoT validation data consisting of 69 and 24 patients, respectively. Of all variables, edrophonium (sensitivity 94%, specificity 90%) and AChR antibody testing (sensitivity 85%, specificity 96%) showed the highest predictive value during validation with an AUC of 0.912 and 0.872, respectively. Incorporating more predictors reduced the predictive error in both validation data sets. CONCLUSIONS: Our prediction model serves as a basis to predict the OMG likelihood. It underwent successful internal and external validation and can be used to assist in clinical decision making.
J Neuroophthalmol
· 2025 Dec · PMID 40198267
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BACKGROUND: Although fluctuating muscular weakness is the hallmark of myasthenia gravis (MG), research into it, especially during the course of the day, remains limited. Understanding the dynamics of myasthenic symptoms...BACKGROUND: Although fluctuating muscular weakness is the hallmark of myasthenia gravis (MG), research into it, especially during the course of the day, remains limited. Understanding the dynamics of myasthenic symptoms is essential for diagnosis and anticipatory treatment. Therefore, in this study, we used orthoptic and other established quantitative and subjective methods to measure ocular myasthenia gravis (OMG) symptoms throughout the day, during the course of 2 months, and in response to treatment. METHODS: The goal of the study was to determine the change of gaze deviation and ptosis during the course of the day, over 2 months, and 1 hour after pyridostigmine intake. Each subject participated in 3 sessions during the day, 2 follow-up sessions, and 1 measurement before and after pyridostigmine. Measurements included the Quantitative Myasthenia Gravis (QMG) score, palpebral fissure height (PFH) photography, the conventional Hess screen test, and a video Hess screen test using video-oculography. The Myasthenia Gravis Activities of Daily Living score (MG-ADL) was obtained on each assessment day. Sum scores were calculated for the gaze deviations of the inner and outer fields of the conventional and the video Hess screen tests. RESULTS: Twelve patients were recruited, including 11 patients with ocular and 1 patient with generalized MG (mean age 65.7 years, SD 16.9 years; 11 males). The mean sum scores of both the conventional and the video Hess screen test showed a worsening in the evening, reaching significance in the outer field of the Hess screen test (mean increase 13.4°, SD 15.3°, P = 0.02). Similarly, ptosis also worsened during the day, with a significant decrease in PFH in the evening (mean decrease 0.53 mm, SD 0.55 mm, P = 0.04). Although ptosis improved significantly after pyridostigmine intake (mean increase 0.96 mm, SD 1.05, P = 0.03), no significant changes were observed in the sum deviations of the Hess screen tests ( P = 0.6). Both ptosis and the sum scores generally improved over the 2-month period, even in some patients without any therapeutic adjustments. Correspondingly, the mean QMG and MG-ADL scores decreased. CONCLUSIONS: This prospective cohort study provides insight into the dynamics of OMG, which is crucial for the optimization of diagnostic and therapeutic approaches. Our orthoptic measurements demonstrated the worsening of OMG symptoms after daily activity and a better response of ptosis to pyridostigmine than diplopia. The complexity of this fluctuating disease leads to strong interindividual variability, which requires an individual approach to improve the quality of life of patients with MG.
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer management by enhancing the immune system's ability to target cancer cells. However, they are known to be associated with immune-related adverse eve...BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer management by enhancing the immune system's ability to target cancer cells. However, they are known to be associated with immune-related adverse events, including ICI-induced myasthenia gravis (ICI-MG). There is limited literature on the isolated ocular form, ICI-induced ocular myasthenia gravis (ICI-OMG). The purpose of this study was to characterize clinical presentation and response to treatment of patients with ICI-OMG. METHODS: This case series and literature review focuses on isolated ICI-OMG. Data collected from patients at 2 North American academic neuro-ophthalmology practices included demographics, ICI type and duration of use, malignancy type, metastasis, symptoms, examination results, and treatment responses. A comprehensive literature review on isolated ICI-OMG cases was also conducted. RESULTS: Our data identified 3 patients with ICI-OMG with bilateral ptosis and diplopia, but no systemic or bulbar involvement at presentation. Literature review found 12 additional cases, with pembrolizumab being the most common ICI associated with OMG. All cases had ptosis, and most had diplopia. Testing for multiple OMG-associated antibodies was often negative and single-fiber electromyography (sfEMG) results varied. Treatments with corticosteroids, intravenous immunoglobulins, plasmapheresis, and pyridostigmine had mixed results. CONCLUSIONS: ICI-OMG is a rare and distinct condition, presenting significant diagnostic challenges due to often negative antibody tests and variable sfEMG results. Early recognition of ICI-OMG in patients with ptosis and/or diplopia is crucial. Treatment responses vary, and most patients do not return to baseline, indicating ICI-OMG is likely chronic. Further research is needed to improve diagnostic markers and treatment strategies.