Visual and Pharmacotherapy Outcomes After Transverse Sinus Stenting for Idiopathic Intracranial Hypertension.

BACKGROUND: Transverse sinus stenting (TSS) is an increasingly common treatment for patients with idiopathic intracranial hypertension (IIH). However, detailed neuro-ophthalmic evidence on visual and pharmacotherapy outcomes after TSS is scarce and heterogeneous. This study aimed to describe the visual outcomes of patients undergoing TSS for IIH and to ascertain the proportion of patients who could be weaned off intracranial pressure (ICP)-lowering medication postoperatively. METHODS: A retrospective chart review of all patients with IIH from 2 tertiary academic neuro-ophthalmology practices who underwent TSS between 2016 and 2022 was performed. Indications for stenting included failure of pharmacotherapy, intolerance of pharmacotherapy, and acute vision loss from severe papilledema. Data on demographics, symptoms, visual function, pharmacotherapy, and TSS were collected. The paired Wilcoxon rank sum test was used to compare changes in visual acuity (VA) and visual field mean deviation (VFMD) between the baseline and most recent visits. RESULTS: Of the 435 patients with IIH, 15 (13 women) met inclusion criteria. After TSS, ICP-lowering pharmacotherapy was discontinued in 10 patients and decreased in 4; 1 patient was not on ICP-lowering medication before TSS. All patients experienced resolution or improvement of symptoms (10 resolution, 4 improved, 1 asymptomatic before TSS) and papilledema (11 resolution, 4 improved) after stenting. Papilledema resolution was confirmed with optical coherence tomography-measured peripapillary nerve fiber layer thickness (median decrease 147 µm, interquartile range 41.8-242.8 µm, P < 0.001). Change in VA between the baseline and most recent visit was not significant, but VFMD improved significantly after stenting (median increase 3.0, IQR 2.0-4.2, P < 0.001). No patient developed transverse sinus restenosis nor in-stent thrombosis postoperatively across a median venogram follow-up of 20.8 (11.3-49.8) weeks. In addition, no patient required subsequent surgical intervention for IIH. CONCLUSIONS: In this cohort of patients with IIH and fulminant presentation, medication resistance, or medication intolerance, TSS was an effective and safe treatment modality. Most patients were able to stop ICP-lowering medications while demonstrating striking improvement in symptomatology and visual function.

Functional vision disorder: a review of diagnosis, management and costs.

Functional vision disorder (FVD) is a relatively common diagnosis in ophthalmic practice which can be difficult to make because of clinician's apprehension to miss organic pathology. We review the diagnostic approach to patients with FVD, organic mimics of FVD, its diagnostic and management strategies and associated cost burden. Patients with FVD typically present with visual acuity and/or field loss. Diagnostic work-up should include patient observation, detailed history, pupillary examination, dilated ophthalmoscopy, visual field testing and ganglion cell analysis of the macular complex. Most common organic mimickers of FVD are amblyopia, cortical blindness, retrobulbar optic neuritis, cone dystrophy and chiasmal tumours; however, all could be ruled out by structured diagnostic approach. For patients with unilateral visual loss, bottom-up refraction, fogging of the well-seeing eye in the phoropter, convex lens and base-down prism tests could aid in diagnosis. For patients claiming binocular vision loss, checking for eye movement during the mirror test or nystagmus elicited by an optokinetic drum can be helpful. Effective management of FVD involves reassurance, stress reduction and, if agreed on, management of comorbid anxiety and/or depression. The social cost of FVD is predominately economic as patients typically meet several healthcare providers over multiple visits and often undergo several neuroimaging studies before neuro-ophthalmology referral. Further, inappropriate granting of disability benefits confers additional stigma to patients with organic vision loss.

Assessment of Reversibility of Transverse Venous Sinus Stenosis in Patients With Papilledema.

BACKGROUND: Bilateral transverse venous sinus stenosis (TVSS) or stenosis of a dominant venous sinus has been found to be very sensitive radiological findings in patients with intracranial hypertension (IH), yet there is still an ongoing debate whether they constitute reversible or permanent phenomena. Thus, the purpose of this study was to investigate the reversibility of TVSS in patients with IH, including conservatively treated patients with signs of IH as defined by the presence of papilledema. METHODS: This was a retrospective chart review of all patients diagnosed with IH between 2016 and 2022, assessed from 2 tertiary university-affiliated neuro-ophthalmology practices. Inclusion criteria were the presence of papilledema, as quantified by optical coherence tomography, and bilateral TVSS, which is considered typical of IH on neuroimaging. During follow-up, included patients must have had confirmation of papilledema resolution as well as subsequent neuroimaging after conservative treatment or cerebrospinal fluid flow diversion. Patients with dural sinus vein thrombosis or intrinsic stenosis from sinus trabeculations or significant arachnoid granulations were excluded from the study. Either CT venography or MRI/MR venography was reviewed by a fellowship-trained neuroradiologist, and the degree of stenosis was scored through the combined conduit score (CCS), as described by Farb et al. The primary outcome was to assess TVSS changes after resolution or improvement of papilledema. RESULTS: From 435 patients, we identified a subset of 10 who satisfied all inclusion criteria. Our cohort comprised entirely women with a median age of 29.5 years and a median BMI of 32.5 kg/m2. Treatment consisted of acetazolamide in 7 patients, of which 1 had additional topiramate and 2 underwent cerebrospinal fluid flow diversion. Furthermore, 6 patients demonstrated significant weight loss during follow-up. For the primary outcome, 5 of 10 patients exhibited no appreciable TVSS change, and 5 patients demonstrated significant improvement in TVSS, of which 4 received conservative treatment only. Papilledema resolution or improvement was statistically significantly associated with increasing average CCS, TVSS diameter, and grade. CONCLUSIONS: We were able to demonstrate that TVSS can be both irreversible and reversible in patients with resolved papilledema. The finding of TVSS reversibility from conservative treatment alone is novel and has important implications to optimize patient care. Future studies should work to identify factors associated with irreversible TVSS for subsequent targeted intervention and prevention.

The Leading Causes of Optic Disc Edema Seen in Tertiary Care, Academic Neuro-Ophthalmology Clinics.

BACKGROUND: Optic disc edema (ODE) is one of the most common reasons for referral to a neuro-ophthalmologist. There are various causes that require vastly different workup. Thus, differentiating among each cause is important. Our goal was to determine the causes of ODE and various clinical characteristics of consecutive patients with ODE presenting to neuro-ophthalmology clinics. METHODS: A retrospective review of consecutive patients with ODE over a period of 5 years were included. Fundus photographs were routinely obtained as part of clinical care. Clinical data including retinal nerve fiber layer thickness, best-corrected visual acuity, and visual field mean deviation were retrieved, and patients were grouped by etiology. RESULTS: A total of 654 patients (n = 462 or 70.6% women and 192 or 29.4% men) with ODE were included with a mean age of 41.2 ± 17.9 years. Female patients were significantly younger than male patients (mean age female participants: 38.7 years, male participants: 47.6; P < 0.001). The top 5 most common causes of ODE in our clinics were idiopathic intracranial hypertension (IIH; 351/654 or 53.7%), nonarteritic anterior ischemic optic neuropathy (NAION; 116/654 or 17.4%), non-IIH papilledema (71/654 or 10.9%), optic neuritis (ON; 46/654 or 7.0%), and uveitis (17/654 or 2.6%). When considering female-only patients, the top 3 causes of ODE were IIH, non-IIH papilledema, and NAION. Among male-only patients, the top 3 causes were NAION, IIH, and non-IIH. Among the top 5 causes of ODE, visual acuity was the worst at presentation in the ON group and the best in the patients with IIH. The Humphrey mean deviation was the worst in ON/NAION groups and best in IIH group. The ODE was most severe in patients with non-IIH papilledema and least severe in ON group. Non-IIH patients with papilledema were not significantly different in visual acuity and visual field parameters at presentation compared with patients with IIH papilledema. Patients with papilledema (both IIH and non-IIH etiologies) had significantly better visual function at presentation compared with other top causes of disc edema (P < 0.001). CONCLUSIONS: The most common cause of ODE seen in neuro-ophthalmology clinics was IIH, and these patients were more likely to present with preserved visual function. The higher prevalence of IIH was likely why most patients with ODE were women. Visual function at presentation was not able to differentiate the specific cause of papilledema; however, it was an important differentiating factor for all papilledema cases compared with all other causes of ODE including ON and NAION.

Utility of ChatGPT for Automated Creation of Patient Education Handouts: An Application in Neuro-Ophthalmology.

BACKGROUND: Patient education in ophthalmology poses a challenge for physicians because of time and resource limitations. ChatGPT (OpenAI, San Francisco) may assist with automating production of patient handouts on common neuro-ophthalmic diseases. METHODS: We queried ChatGPT-3.5 to generate 51 patient education handouts across 17 conditions. We devised the "Quality of Generated Language Outputs for Patients" (QGLOP) tool to assess handouts on the domains of accuracy/comprehensiveness, bias, currency, and tone, each scored out of 4 for a total of 16. A fellowship-trained neuro-ophthalmologist scored each passage. Handout readability was assessed using the Simple Measure of Gobbledygook (SMOG), which estimates years of education required to understand a text. RESULTS: The QGLOP scores for accuracy, bias, currency, and tone were found to be 2.43, 3, 3.43, and 3.02 respectively. The mean QGLOP score was 11.9 [95% CI 8.98, 14.8] out of 16 points, indicating a performance of 74.4% [95% CI 56.1%, 92.5%]. The mean SMOG across responses as 10.9 [95% CI 9.36, 12.4] years of education. CONCLUSIONS: The mean QGLOP score suggests that a fellowship-trained ophthalmologist may have at-least a moderate level of satisfaction with the write-up quality conferred by ChatGPT. This still requires a final review and editing before dissemination. Comparatively, the rarer 5% of responses collectively on either extreme would require very mild or extensive revision. Also, the mean SMOG score exceeded the accepted upper limits of grade 8 reading level for health-related patient handouts. In its current iteration, ChatGPT should be used as an efficiency tool to generate an initial draft for the neuro-ophthalmologist, who may then refine the accuracy and readability for a lay readership.

Sex or Gender Reporting in Ophthalmology Clinical Trials Among US Food and Drug Administration Approvals, 1995 to 2022.

Importance: As critical determinants of scientific rigor, reproducibility, and equity, sex and gender should be considered in clinical trial design and reporting. Objective: To evaluate the accuracy of sex and gender reporting and extent of sex- and gender-based analysis in clinical trials associated with US Food and Drug Administration (FDA) drug approvals between January 1, 1995, and December 31, 2022. Design, Setting, and Participants: In this cross-sectional study of participants enrolled in FDA ophthalmology trials, the following trial documents were reviewed by pairs of independent reviewers in decreasing order of priority: peer-reviewed publication, ClinicalTrials.gov report, and FDA medical and statistical reviews. Trial protocols and supplementary materials were also reviewed. Main Outcome and Measures: The proportion of trials that correctly applied sex and gender terminology, reported the method of assessing sex or gender, and conducted sex- or gender-based data analysis; incorrect application of sex and gender terminology was defined as interchangeable use of sex- and gender-related terms without a clear justification. Results: Between 1995 and 2022, 34 ophthalmic drugs corresponding to 85 trials (34 740 participants) received FDA approval, of which 16 drugs (47.1%) corresponding to 32 trials (18 535 participants [37.6%]) were associated with peer-reviewed publications. Sixteen trials used sex and gender terminology correctly (19.5%). No trial reported how sex and gender were collected nor enrolled participants from sexual and gender identity minority populations. Most trials reported sex- and gender-disaggregated demographic data (96.5%), but few conducted sex- or gender-based analysis for data on dropout (1.2%), primary outcomes (28.2%), secondary outcomes (2.4%), and adverse events (9.4%). Erroneous sex and gender reporting was associated with later publication year (2008.5 vs 2001.0; median difference, 7.5; 95% CI, -6.0 to 11.0; P < .001) and higher journal influence metrics, including 2022 journal impact factor (13.7 vs 5.9; median difference, 7.8; 95% CI, -1.4 to 152.4, P < .001) and 2022 journal citation indicator (4.9 vs 2.1; median difference, 2.9; 95% CI, 0-20.0, P < .001). Conclusions and Relevance: In this observational study, over three-quarters of ophthalmology trials associated with FDA drug approvals conflated sex and gender and over two-thirds lacked sex- and gender-based analyses. More rigorous integration of sex and gender appears warranted for FDA, and presumably other trials, to improve their validity, reproducibility, and equity.

Sensitivity of Magnetic Resonance Imaging of the Medial Longitudinal Fasciculus in Internuclear Ophthalmoplegia.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a result of insult to the medial longitudinal fasciculus (MLF). Clinicoradiological correlation in patients with INO has been reported to be poor; however, prior studies have used low resolution MRI imaging techniques and included patients with subclinical INO. We aimed to determine the sensitivity of modern MRI interpreted by a specialist neuroradiologist to detect clinically evident INO. METHODS: A retrospective chart review of patients in 2 tertiary University-affiliated neuro-ophthalmology practices with the diagnosis of INO. MRI scans of all patients were reviewed and interpreted by a fellowship-trained neuroradiologist for the presence of lesion in MLF and concordance with the original imaging report. RESULTS: Forty-five patients were included in the study: 33 with demyelinating disease, 11 with stroke, and 1 with intracranial mass. A visible MLF lesion was present in 25/33 demyelinating cases and 7/11 ischemic cases. Lesions in 2 cases in each group were identified only after review by a fellowship-trained neuroradiologist. In demyelinating INO, patients with a visible MLF lesion were more likely to show other brainstem (72%) and supratentorial (51%) white matter lesions. CONCLUSIONS: In 25% of patients with demyelinating INO and 33% of patients with ischemic INO, no visible lesion was identified on current high-quality MRI imaging. Review of imaging by a neuroradiologist increased the possibility of lesion been identified.

Anti-Ma2 Antibody-Mediated Paraneoplastic Cerebellar Degeneration and Myeloneuropathy Secondary to Lymphoma.

ABSTRACT: A 61-year-old woman with a history of untreated low-grade B-cell lymphoma presented with blurry vision, unsteadiness, and worsening pain on touching skin of the upper trunk was enrolled. Blurry vision was attributed to oscillopsia from downbeat nystagmus, which later evolved into macrosaccadic oscillations. MRI brain and spine showed mild, longitudinally extensive T2 hyperintensity in the central gray matter of the spinal cord extending from the medulla to T11 level. Serum paraneoplastic panel was negative; however, she had very high titers of anti-Ma2 antibodies in cerebrospinal fluid. The diagnosis of paraneoplastic neurological syndrome was made. Empiric treatment with high dose of intravenous steroids followed by intravenous immunoglobulin infusions did not improve her symptoms. An extensive search for an underlying tumor commenced and was initially unrevealing. However, two-month follow-up positron emission tomography scan showed increased uptake in a right pulmonary nodule, which when biopsied confirmed diagnosis of extranodal marginal zone lymphoma. The final diagnosis was anti-Ma2 antibody-mediated paraneoplastic cerebellar degeneration and myeloneuropathy secondary to lymphoma.

Yield of Investigations in Young Patients Presenting With Transient Monocular Vision Loss: A Prospective Study.

PURPOSE: It is unclear whether transient monocular vision loss (TMVL) warrants the same thorough systemic evaluation for potential embolic sources in young adults as it does in older adults. The objective of the present study was to evaluate the yield of investigations in patients under 45 years of age presenting with TMVL. DESIGN: Prospective cohort study. METHODS: Young adult patients with TMVL presenting to a university-affiliated neuro-ophthalmology clinic were included. All included patients were referred for neuroimaging (computed tomography or magnetic resonance angiography of entire carotid tree and magnetic resonance imaging of the brain) and cardiac investigations (transesophageal echocardiography and 2 weeks of Holter monitoring). RESULTS: A total of 20 participants with TMVL were included in the study. The mean age was 33.1 ± 8.2 years, and 16 of the 20 participants were women. The most common finding on past medical history was migraines, in 5 of 20 cases (25%), and 25% of patients had headaches during their visual loss. Of 17 participants who completed neuroimaging, 1 had fibromuscular dysplasia (this patient also experienced headaches during their symptoms). Two of 13 patients who completed echocardiography had patent foramen ovale. Overall, 3 of 20 participants (15%, 95% CI 3%-38%) had abnormal findings associated with their TMVL. Aspirin treatment was initiated in 2 of 3 patients following investigations. CONCLUSION: In our cohort of young patients presenting with TMVL, 15% of patients had abnormal findings on further investigations. We recommend that young patients presenting with TMVL be referred for neuroimaging and cardiac workup so that appropriate treatments can be initiated to prevent future complications. Headaches during vision loss may not always indicate a benign cause, and retinal migraine should be a diagnosis of exclusion.

The Causes of Optic Disc Edema in Patients Presenting With Significantly Compromised Vision.

BACKGROUND: To evaluate the most common causes of optic disc edema (ODE) in patients with significantly compromised vision (initial best-corrected visual acuity [BCVA] of 20/400 or worse) at presentation. METHODS: Retrospective chart review over a 5-year period of consecutive patients presenting to tertiary neuro-ophthalmology clinics at the University of Toronto. RESULTS: A total of 656 patients with ODE were included, and 49 patients (7.47%) had an initial BCVA of 20/400 or worse. There were 54 eyes included at baseline and 49 eyes at final follow-up. There were 29 female and 20 male patients. The mean age at first visit across patients was 55.9 years. Female patients (n = 29) were significantly older than male patients (n = 20) (P < 0.05). The causes of ODE were optic neuritis (ON) (n = 22; 40.7%), nonarteritic anterior ischemic optic neuropathy (NAION) (n = 22; 40.7%), arteritic anterior ischemic optic neuropathy (AAION) (n = 5; 9.26%), uveitis-related (n = 3; 5.56%), papilledema from idiopathic intracranial hypertension (IIH) (n = 1; 1.85%), and Vogt-Koyanagi-Harada disease (n = 1; 1.85%). Initial BCVA was not significantly different between ON and NAION groups (P = 0.52); however, final BCVA was significantly better in the ON group (P < 0.0001). The mean initial BCVA was worst in the AAION group (2.62 ± 0.54 logarithm of the minimum angle of resolution). The most common cause of ODE in patients <40 years old was ON (83.3%), whereas the 2 most common causes in patients >80 were NAION (60%) and AAION (40%). In patients between the ages of 60-80, NAION (100%) was the only cause. CONCLUSIONS: Patients with ODE and poor vision at presentation represent a minority of cases seen in neuro-ophthalmology clinics (<10%). Optic neuritis and NAION are the 2 most common causes of ODE with poor vision at presentation. These findings are limited by a small sample size and potential sampling bias.