BACKGROUND: Despite advances in clarifying hormonal and metabolic factors relevant to the pathophysiology of idiopathic intracranial hypertension (IIH), its mechanism remains incompletely defined. Recognition of the glym...BACKGROUND: Despite advances in clarifying hormonal and metabolic factors relevant to the pathophysiology of idiopathic intracranial hypertension (IIH), its mechanism remains incompletely defined. Recognition of the glymphatic system in 2012 fostered several hypotheses regarding roles it might play in IIH. This State-of-the-Art Review describes the glymphatic system's anatomy and physiology, factors relevant both to the glymphatic system and IIH, methods of obtaining experimental evidence, and how the existing evidence has tested and shaped hypotheses relating glymphatic transit and IIH. EVIDENCE ACQUISITION: A literature search was conducted on December 10, 2025, to identify publications related to the glymphatic system in IIH, using PubMed, Embase, Web of Science, and the Cochrane Library. Snowballing and reverse snowballing were used to identify additional references relevant to explicitly stated links between the glymphatic system and IIH. References were screened using Covidence by 2 independent reviewers. RESULTS: One hundred thirty-six records were identified; 60 were duplicate, 27 were excluded in screening due to lack of applicability. Among the 49 retrieved, 17 were excluded due to incorrect patient population (8), reviews without critique, expert opinion, or new hypotheses (8), or language (1). Thirty-two were included in this review. CONCLUSIONS: Three categories of hypothesis relating to glymphatic transit in IIH were identified in the literature: (1) glymphatic dysfunction causes IIH, (2) veno-glymphatic dysfunction causes IIH, and (3) glymphatic function is altered but adaptive in IIH with clinical decompensation when its fluid transit capacity is overwhelmed. While glymphatic transit seems not to be normal in IIH, recent evidence suggesting dynamic transit across the disease course without clear correlation with intracranial pressure favors a novel hypothesis: that glymphatic changes may be secondary to IIH without playing a central role in its pathogenesis. Further prospective and ideally multimodal work is required, taking into account an increasing number of potentially relevant variables which may influence glymphatic transit in IIH, including disease duration, venous sinus stenosis, and treatment status.
BACKGROUND: Idiopathic intracranial hypertension without papilledema (IIHWOP) remains poorly understood. This review summarizes the diagnostic challenges and potential management of adults with IIHWOP. EVIDENCE ACQUISITI...BACKGROUND: Idiopathic intracranial hypertension without papilledema (IIHWOP) remains poorly understood. This review summarizes the diagnostic challenges and potential management of adults with IIHWOP. EVIDENCE ACQUISITION: A detailed search of the scientific literature, combining MeSH and free-text terms, included all English-language papers on PubMed, from inception to June 8, 2025. In this review, we used the term IIHWOP to describe patients without evidence of active or previous papilledema. RESULTS: The diagnosis of IIHWOP is based on elevated lumbar puncture opening pressure accompanied by either sixth cranial nerve palsy or neuroimaging features of intracranial hypertension, which may lack specificity. Clinical presentation frequently mimics primary headache disorders, and lumbar puncture remains an invasive procedure without clear management implications in IIHWOP, as there are no high-quality studies evaluating medical or surgical therapies. CONCLUSIONS: Recommendations for investigation and clinical care remain largely inferred from idiopathic intracranial hypertension. Given the absence of evidence for risk of vision loss, invasive procedures should be avoided, and management should focus on weight loss and optimized headache management.
BACKGROUND: This study evaluates the feasibility and acceptability of a virtual reality platform (VRP) for home monitoring of visual function in patients with neuro-ophthalmic conditions. METHODS: Fifteen patients with n...BACKGROUND: This study evaluates the feasibility and acceptability of a virtual reality platform (VRP) for home monitoring of visual function in patients with neuro-ophthalmic conditions. METHODS: Fifteen patients with nonarteritic anterior ischemic optic neuropathy (NAAION), optic neuritis, or papilledema were enrolled and monitored remotely over 12 weeks. Visual acuity, color vision, and visual field testing were collected 3 times per week using the VRP. Compliance and satisfaction levels were analyzed. RESULTS: A total of 21 eyes were included (38.1% NAAION, 42.9% optic neuritis, 19% papilledema). Most participants (71.4%) found weekly VRP use easy, and all felt confident using it at home. While 86% reported no technical issues, 21%-28% experienced transient symptoms such as blurred vision or dizziness. Compliance was highest in the NAAION group, with 75% completing the full 12-week period. In the optic neuritis group, 55.6% remained after Week 1 and 44.4% continued through Week 8. The papilledema group discontinued by Week 4. Main reasons for discontinuation included time constraints, scheduling conflicts, and stable vision after improvement. In general, visual acuity and visual field indices (mean deviation and pattern SD [PSD]) showed no significant changes over time, confirming good VRP'S reproducibility for home monitoring. This VRP also detected cases of visual function worsening, enabling earlier rescheduling of clinical appointments. CONCLUSION: The VRP is a feasible and well-accepted tool for home-based visual monitoring in neuro-ophthalmic patients as an alternative to in-person eye examinations. This approach enables early detection of changes and can improve long-term management.
BACKGROUND: Contemporary literature suggests that anemia may be a risk factor for the development of pseudotumor cerebri (PTC) and associated with poorer visual outcomes. However, literature describing the association is...BACKGROUND: Contemporary literature suggests that anemia may be a risk factor for the development of pseudotumor cerebri (PTC) and associated with poorer visual outcomes. However, literature describing the association is limited, and whether laboratory testing for anemia should be done during a PTC work-up is frequently debated among neuro-ophthalmologists. METHODS: International Classification of Diseases-10 codes were used to identify patients with PTC from the SOURCE database. Patients with PTC were matched for age, sex, and race with controls. Relative rates of anemia were compared between groups. A subgroup analysis compared demographic factors and outcomes for PTC patients with and without anemia. RESULTS: Two-thousand two-hundred forty patients with PTC and 2,240 age-, race-, body mass index-, and sex-matched controls from a national, multicentered database were included in the study. Rates of anemia did not differ between PTC and non-PTC groups (23.4% vs 22.3%, P = 0.393). Among patients with PTC, anemia was associated with older age at onset (38.0 ± 14.1 vs 36.1 ± 13.6 [27.0-45.0] years, P = 0.013), male sex (16.2% vs 10.7%, P = 0.017), and lower visual acuity at presentation ( P < 0.001), but final visual acuities were similar when controlling for presenting acuity ( P = 0.123). CONCLUSIONS: Using the largest sample of patients with PTC and matched controls to date, anemia was not associated with PTC diagnosis. Among patients with PTC, anemia was associated with demographic features atypical for PTC.
BACKGROUND: Heavy eye syndrome (HES) is characterized by progressive esotropia and hypotropia with high myopia. Diagnosis is based on the clinical presentation and is often supported by imaging. In this study we describe...BACKGROUND: Heavy eye syndrome (HES) is characterized by progressive esotropia and hypotropia with high myopia. Diagnosis is based on the clinical presentation and is often supported by imaging. In this study we describe a novel clinical sign observed in patients with HES. METHODS: We conducted a cross-sectional, retrospective analysis of patients with limitation in elevation in adduction, examined between February 2025 and June 2025. Examinations were not masked to diagnosis. Presence of the Abduction-Release Sign on examination was recorded and compared between patients with HES and those with other diagnoses who served as controls. The sign is elicited when the patient is asked to abduct the eye, then in a slow circular motion bring the eye upward and into an adducted position. RESULTS: We identified 14 cases with limitation in elevation in which the sign was tested. Four had HES and 10 had other diagnoses (60% had thyroid eye disease, 20% had Brown syndrome, and 20% other diagnoses). Mean spherical equivalent was -17.8 ± 8.0 D in the HES group and +0.17 ± 2.3 D in the control group. Of the 4 patients with HES, all had a positive Abduction-Release Sign on examination, compared with none in the control group (P = 0.001). CONCLUSIONS: Among this cohort of patients with limitation in elevation, the presence of the Abduction-Release Sign was significantly associated with HES. This examination finding might be useful in the evaluation of patients with HES together with traditional examination and imaging findings. Its utility may be limited in severe cases, because abduction may be insufficient to elicit the sign. It might also offer insights into the structural and functional changes that occur in this syndrome.
BACKGROUND: Uveitis and optic neuritis related to demyelinating disease share similar immune mechanisms and can have deleterious visual consequences. Data on uveitis incidence in patients with central nervous system (CNS...BACKGROUND: Uveitis and optic neuritis related to demyelinating disease share similar immune mechanisms and can have deleterious visual consequences. Data on uveitis incidence in patients with central nervous system (CNS) demyelinating diseases remain limited. Our objective was to assess the 5-year incidence of uveitis among patients with CNS demyelinating diseases with and without optic neuritis. METHODS: Retrospective cohort study using a health records aggregate. We identified patients aged ≥18 years using diagnostic codes to arrange into 3 study groups: a composite CNS demyelinating disease cohort, a multiple sclerosis (MS) cohort, and a neuromyelitis optica/myelin oligodendrocyte glycoprotein antibody-associated disease cohort, each stratified by presence or absence of optic neuritis. We matched each study group based on demographics, clinical comorbidities, medications, and encounter visits. RESULTS: After matching, the 5-year cumulative incidence of any uveitis among patients with optic neuritis in the CNS demyelinating disease group was 1.09% (95% confidence intervals [CI] 0.950-1.25) compared with 0.610% (95% CI 0.501-0.743) in those without optic neuritis (log-rank P < 0.0001), with a hazard ratio (HR) of 1.99 (95% CI 1.57-2.52). The 5-year cumulative incidence of any uveitis among patients with optic neuritis in patients with MS was 0.986% (95% CI 0.846-1.15) compared to 0.543% (95% CI 0.437-0.676) in those without optic neuritis (log-rank P < 0.0001), with a HR of 1.95 (95% CI 1.51-2.53). Although patients with neuromyelitis optica/myelin oligodendrocyte glycoprotein antibody-associated disease showed similar trends, there was no statistical significance. Intermediate uveitis demonstrated the strongest associations with optic neuritis across study groups. CONCLUSIONS: Optic neuritis is a clinically meaningful risk factor for uveitis in patients with CNS demyelinating disease, underscoring the need for careful ophthalmic surveillance in this population.
BACKGROUND: Giant cell arteritis (GCA) has traditionally been recognized as more common in White populations, but there is limited understanding of its epidemiology and severe ischemic manifestations in other racial and...BACKGROUND: Giant cell arteritis (GCA) has traditionally been recognized as more common in White populations, but there is limited understanding of its epidemiology and severe ischemic manifestations in other racial and ethnic groups. This study investigated racial and ethnic differences in GCA ischemic manifestations and tocilizumab use. METHODS: We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Age- and sex-matched cohorts of non-Hispanic White (hereafter referred to as White), non-Hispanic Black or African American (Black), non-Hispanic Asian (Asian), and Hispanic or Latino (Hispanic) patients diagnosed with GCA were analyzed for differences in severe clinical manifestations within 1 month of GCA diagnosis (ischemic optic neuropathy, blindness/low vision, central retinal artery occlusion, stroke, aortic aneurysm and dissection, acute myocardial infarction) and tocilizumab use within 1 year. RESULTS: Compared with White patients, Black patients had lower odds of ischemic optic neuropathy (odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.33-0.65), higher stroke risk (OR: 1.68, 95% CI: 1.16-2.43), and were less likely to receive tocilizumab (OR: 0.44, 95% CI: 0.33-0.59). Hispanic patients had lower odds of ischemic optic neuropathy (OR: 0.61, 95% CI: 0.37-0.98) and receiving tocilizumab (OR: 0.51, 95% CI: 0.34-0.74) compared with White patients. Additionally, compared with White patients, Asian patients were less likely to be diagnosed with blindness/low vision (OR: 0.45, 95% CI: 0.27-0.76), had similar odds of ischemic optic neuropathy, and had no significant differences in tocilizumab use. CONCLUSIONS: There may be significant differences in severe ischemic manifestations of GCA among non-White patients compared with White patients. There also appear to be differences in treatment with tocilizumab between Black and White patients and between Hispanic and White patients, but not between Asian and White patients.
BACKGROUND: This study evaluated time-of-day differences in intraocular pressure (IOP), mean arterial pressure (MAP), and ocular perfusion pressure (OPP) in eyes affected by nonarteritic anterior ischemic optic neuropath...BACKGROUND: This study evaluated time-of-day differences in intraocular pressure (IOP), mean arterial pressure (MAP), and ocular perfusion pressure (OPP) in eyes affected by nonarteritic anterior ischemic optic neuropathy (NAION), and compared these measures between NAION-affected and unaffected eyes at each time period. METHODS: Adults aged 18-90 years with a confirmed diagnosis of NAION were enrolled in this nonrandomized prospective observational cohort study. Participants were trained to measure blood pressure (BP) and IOP using an automated BP cuff and the iCare HOME2 rebound tonometer. In participants with only 1 eye affected by NAION, the unaffected eye was used as a control. Measurements were collected at 7 predefined daily time points (4:00, 6:00, 9:00, 12:00, 15:00, 18:00, and 21:00) for at least 7 consecutive days. MAP and OPP were calculated as 1/3 systolic + 2/3 diastolic pressure and 2/3 × (MAP - IOP), respectively. Early morning (4:00, 6:00), midday (9:00, 12:00, 15:00), and evening (18:00, 21:00) measurements were compared using linear mixed-effects models. The main outcome measures were intraday measurements of IOP, MAP, and OPP. RESULTS: A total of 27 eyes of 15 patients were included in the study. Among NAION-affected eyes, mean OPP and MAP were lowest in the early morning. No IOP elevations were noted in the early waking hours. On average, OPP was 1.69 mm Hg higher and MAP was 2.70 mm Hg higher at midday than in the morning, while IOP increased by 0.76 mm Hg (all 95% confidence interval [CI]). In the evening, OPP was 1.83 mm Hg higher and MAP was 2.49 mm Hg higher than in the morning (both 95% CI). Evening IOP was 0.31 mm Hg lower than in the morning, but this difference was not statistically significant ( P = 0.08). CONCLUSIONS: Early morning low OPP in nonglaucomatous eyes with NAION seems to be correlated with low MAP, rather than elevated IOP. These findings help support a role for impaired local perfusion in the early waking hours in the pathogenesis of NAION and highlight the potential utility of IOP and BP diurnal monitoring in at-risk patients.
BACKGROUND: In July 2024, a matched cohort study reported an association between semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), and nonarteritic anterior ischemic optic neuropathy (NAION), a rare opt...BACKGROUND: In July 2024, a matched cohort study reported an association between semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), and nonarteritic anterior ischemic optic neuropathy (NAION), a rare optic neuropathy. The study prompted widespread media coverage. Given the media's role in shaping perceptions of drug safety, we conducted a content analysis of news reporting on this association. METHODS: We performed a qualitative content analysis of English-language news articles published between July 3, 2024, and March 31, 2025. Articles were retrieved through LexisNexis and included if they discussed both GLP-1 RAs and NAION in a public-facing context. Articles were coded by 3 independent reviewers using a structured tool to assess scientific accuracy, causal language, framing of certainty, citation of the original study, quoted sources, and emotive or misleading language. RESULTS: Seventy-one articles met inclusion criteria. Twenty-one percent used causal language, 80% used scientific language, and 48% contained misleading claims. Articles with causation errors were less likely to correctly define NAION (73% vs 92%), quote physicians (33% vs 63%), or mention study limitations (27% vs 66%). US articles had the lowest rate of causation errors (5%) and UK. articles had the highest (34%). CONCLUSIONS: Media coverage of the potential semaglutide-NAION link varied in accuracy and tone. Articles avoiding causation errors more often included expert input and contextualized uncertainty. These findings highlight the need for responsible health journalism in reporting emerging safety concerns.