The Occurrence of Intraretinal and Subretinal Fluid in Anterior Ischemic Optic Neuropathy: Pathogenesis, Prognosis, and Treatment.

PURPOSE: To describe the frequency and characteristics of intraretinal and subretinal fluid in nonarteritic anterior ischemic optic neuropathy (NAAION) and to assess the influence on the visual deficit and optic nerve fiber/ganglion cell loss. DESIGN: A retrospective, single-center study. PARTICIPANTS: Thirty-two patients with NAAION referred to our Neuro-ophthalmology Department between 2014 and 2021. METHODS: The study was carried out at the University Hospital of Liège, Belgium. For participants in whom subretinal fluid was identified on standard OCT (Carl Zeiss Meditec) an additional macular OCT (Spectralis Heidelberg) had been performed. The pattern and the maximal height of the retinal fluid were determined manually, and thicknesses of retinal layers were obtained using the OCT protocol analysis. RESULTS: The mean age of the cohort was 60 years (standard deviation, ±12.5; range, 22-88 years), and 65.6% were male. In the 21 eyes (46.7%) in which retinal fluid was observed, macular OCT findings were categorized according to fluid localization: 19 cases had parafoveal fluid (of whom 9 also had subfoveal fluid). One patient had subfoveal fluid alone, and 1 patient had peripapillary subretinal fluid alone. Specific patterns of optic disc (OD) swelling were associated with the occurrence and distribution of retinal edema. Visual acuity, visual field loss, and foveal thresholds were stable over the period of observation (P = 0.74, P = 0.42, and P = 0.36, respectively). No difference was found in visual function at 6 months between patients with retinal fluid treated (n = 10) or not treated (n = 11) with corticosteroids (visual acuity, P = 0.13; foveal threshold, P = 0.59; mean deviation, P = 0.66). CONCLUSIONS: Subretinal fluid is found in a high proportion of cases of NAAION. Visual function remained largely stable from presentation in this cohort. Corticosteroid intake at presentation did not influence visual recovery or timing of the resorption of tissue edema. Our findings do not support treatment of NAAION with corticosteroids with or without evidence of subretinal fluid acutely. With regard to pathogenesis, we propose that the volume of transudate generated at the OD is the critical factor rather than dysfunction of retinal mechanisms subserving reabsorption. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Differentiating glaucoma from chiasmal compression using optical coherence tomography: the macular naso-temporal ratio.

BACKGROUND/AIMS: The analysis of visual field loss patterns is clinically useful to guide differential diagnosis of visual pathway pathology. This study investigates whether a novel index of macular atrophy patterns can discriminate between chiasmal compression and glaucoma. METHODS: A retrospective series of patients with preoperative chiasmal compression, primary open-angle glaucoma (POAG) and healthy controls. Macular optical coherence tomography (OCT) images were analysed for the macular ganglion cell and inner plexiform layer (mGCIPL) thickness. The nasal hemi-macula was compared with the temporal hemi-macula to derive the macular naso-temporal ratio (mNTR). Differences between groups and diagnostic accuracy were explored with multivariable linear regression and the area under the receiver operating characteristic curve (AUC). RESULTS: We included 111 individuals (31 with chiasmal compression, 30 with POAG and 50 healthy controls). Compared with healthy controls, the mNTR was significantly greater in POAG cases (ß=0.07, 95% CI 0.03 to 0.11, p=0.001) and lower in chiasmal compression cases (ß=-0.12, 95% CI -0.16 to -0.09, p<0.001), even though overall mGCIPL thickness did not discriminate between these pathologies (p=0.36). The mNTR distinguished POAG from chiasmal compression with an AUC of 95.3% (95% CI 90% to 100%). The AUCs when comparing healthy controls to POAG and chiasmal compression were 79.0% (95% CI 68% to 90%) and 89.0% (95% CI 80% to 98%), respectively. CONCLUSIONS: The mNTR can distinguish between chiasmal compression and POAG with high discrimination. This ratio may provide utility over-and-above previously reported sectoral thinning metrics. Incorporation of mNTR into the output of OCT instruments may aid earlier diagnosis of chiasmal compression.

Anticholinergic syndrome: blurred vision and headache.

A young woman presented with blurred vision due to anticholinergic syndrome. We highlight the importance of considering this condition in the context of multiple medications and increased anticholinergic burden. The documented pupil abnormality gives an opportunity to review the syndrome of the reverse (inverse) Argyll Robertson pupil (preserved pupil light response with loss of accommodation). We review other situations in which the reverse Argyll Robertson pupil may occur and its possible mechanism in this case.

Nonarteritic Anterior Ischemic Optic Neuropathy: Cystic Change in the Inner Nuclear Layer Caused by Edema and Retrograde Maculopathy.

Purpose: Microcystic macular edema (MME), also known as retrograde maculopathy (RM), is associated with severe optic atrophy because of a range of causes. However, similar changes have also been described in primary retinal pathology and the pathogenesis of MME is debated. Design: A retrospective observational case series. Participants: Patients with nonarteritic ischemic optic neuropathy. Methods: A retrospective observational case series was performed at the University Hospital of Liège, Belgium. The medical records of patients who were referred to our Neuro-ophthalmology department with a diagnosis of nonarteritic anterior ischemic optic neuropathy (NA-AION), between 2014 and 2021, were reviewed. Main Outcome Measures: Ganglion cell complex thickness, acute and chronic inner nuclear change. Results: In a cohort of 34 patients (mean age: 60 ± 12.5 years; 65.6% men) with NA-AION, we identified a transient microcystic change in the inner nuclear layer (INL) associated with optic disc swelling in 19 eyes at presentation. This early change was associated with a transudate of intraretinal and subretinal fluid originating from the optic disc. Among patients who had shown this transient change 3 subsequently developed MME, which remained fixed during the period of observation (range, 12-34 months). No MME was observed in patients without an early INL transient change. Microcystic macular edema was observed in patients with severe ganglion cell complex thinning at 6 months: mean (± SD) loss in superior hemimacula (-28.2 ± 5.2 µm [-33.3%, range, -22.3 to -30.3 µm]) and in inferior hemimacula (-30.7 ± 5.6 µm [-31.0%, range, -24.3 to 34.8 µm]). Conclusions: Our study has revealed 2 causes of INL cystic change in the same patients experiencing NA-AION, 1 reversible and the other likely permanent. This finding highlights the distinction between genuine edema related to transudation of fluid (in this case secondary to ischemic optic disc swelling) and the phenomenon observed in RM that is related to the degree of retinal nerve fiber layer/ganglion cell complex thinning. Cystic change in the INL is associated with severe optic atrophy (MME). However, similar changes have been described in retinal pathology and the pathogenesis of MME is debated.

Optic neuritis with potential for poor outcome.

The Optic Neuritis Treatment Trial previously reported that corticosteroids accelerated visual recovery in optic neuritis (ON) without improving outcome. This finding related largely to multiple sclerosis (MS), and subsequently neurologists tended to await spontaneous recovery in ON. Since then, non-MS cases of ON have been identified with antibodies to aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG). These disorders can closely mimic multiple sclerosis-associated or idiopathic demyelinating optic neuritis (MS/IDON) initially but risk a worse visual outcome. Scrutinising the clinical features and neuroimaging often enables differentiation between MS/IDON and other causes of ON. Early treatment with high-dose corticosteroids is an important determinant of visual outcome in non-MS/IDON. Prompt use of plasma exchange may also save sight. In this review, we contrast the presentations of myelin oligodendrocyte glycoprotein associated optic neuritis (MOG-ON) and aquaporin 4 associated optic neuritis (AQP4-ON) with MS/IDON and provide an approach to acute management while awaiting results of antibody testing.

Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom.

IMPORTANCE: Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling. OBJECTIVE: To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021. EXPOSURES: Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index. MAIN OUTCOMES AND MEASURES: Multiple sclerosis case status and mGCIPL thickness. RESULTS: A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted ß = -3.09 [95% CI, -5.70 to -0.48] µm; P = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (ß = -0.93 [95% CI, -1.07 to -0.79] µm; P < .001), but there was no statistically significant association in individuals with MS (ß = -2.27 [95% CI, -4.76 to 0.22] µm; P = .07). Smoking was not associated with mGCIPL thickness in MS. However, smoking was associated with greater mGCIPL thickness in control individuals (ß = 0.89 [95% CI, 0.74-1.05 µm]; P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that high alcohol intake was associated with retinal features indicative of more severe neurodegeneration, whereas smoking was associated with higher odds of being diagnosed with MS.

Bilateral optic neuritis as a first presentation of lymph node tuberculosis.

Tuberculosis (TB) may affect the nervous system in many ways. We describe an immunocompetent teenage girl with lymph node TB who had first presented with bilateral optic neuritis. Detailed history identified features inconsistent with immune-mediated optic neuritis. Several unusual features prompted further investigation, including transient visual obscurations without raised intracranial pressure, prominent disc swelling and absence of laboratory findings to support an immune-mediated cause. Whole body PET/MR imaging identified widespread mediastinal and supraclavicular lymphadenopathy. Despite no known TB contacts, a negative interferon gamma release assay and a normal chest X-ray, a targeted lymph node biopsy confirmed TB.

Photophobia in migraine: A symptom cluster?

Photophobia is one of the most common symptoms in migraine, and the underlying mechanism is uncertain. The discovery of the intrinsically-photosensitive retinal ganglion cells which signal the intensity of light on the retina has led to discussion of their role in the pathogenesis of photophobia. In the current review, we discuss the relationship between pain and discomfort leading to light aversion (traditional photophobia) and discomfort from flicker, patterns, and colour that are also common in migraine and cannot be explained solely by the activity of intrinsically-photosensitive retinal ganglion cells. We argue that, at least in migraine, a cortical mechanism provides a parsimonious explanation for discomfort from all forms of visual stimulation, and that the traditional definition of photophobia as pain in response to light may be too restrictive. Future investigation that directly compares the retinal and cortical contributions to photophobia in migraine with that in other conditions may offer better specificity in identifying biomarkers and possible mechanisms to target for treatment.

Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.

Importance: Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse. Objective: To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom. Design, Setting, and Participants: This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls. Exposures: Optic neuritis. Main Outcomes and Measures: Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs. Results: A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28). Conclusions and Relevance: The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.

The role of intracranial pressure in glaucoma and therapeutic implications.

Despite glaucoma being the second leading cause of blindness globally, its pathogenesis remains incompletely understood. Although intraocular pressure (IOP) contributes to glaucoma, and reducing IOP slows progress of the disease, some patients progress despite normal IOP (NTG). Glaucomatous damage causes characteristic cupping of the optic nerve where it passes through the lamina cribrosa. There is evidence that cerebrospinal fluid (CSF) within the optic nerve sheath has a different composition from CSF surrounding the brain. Furthermore, fluctuations in CSF flow into the optic nerve sheath may be reduced by trabeculae within the sheath, and on standing intracranial pressure (ICP) within the sheath is stabilised at around 3 mmHg due to orbital pressure. Blood pressure has been linked both to glaucoma and ICP. These facts have led some to conclude that ICP does not play a role in glaucoma. However, according to stress formulae and Laplace's Law, stress within the lamina cribrosa is dependent on the forces on either side of it, (IOP and ICP), and its thickness. On lying flat at night, ICP between the brain and optic nerve sheath should equalise. Most evidence suggests ICP is lower in glaucoma than in control groups, and that the lamina cribrosa is thinner and more posteriorly displaced in glaucoma. Subjects who have had ICP reduced have developed signs of glaucoma. This review finds most evidence supports a role for low ICP in the pathogenesis of glaucoma. Caffeine, theophylline and vitamin A may increase ICP, and could be new candidates for an oral treatment.