Glaucoma: what the neurologist needs to know.

Glaucoma is a progressive optic neuropathy resulting from pathological changes at the optic disc due to elevated intraocular pressure. Its diagnosis, treatment and follow-up are almost entirely conducted in ophthalmology clinics, with screening conducted by community optometrists. Despite this, neurologists may encounter glaucoma in both its acute presentation (as angle closure, presenting as acute headache) and its chronic forms (often as optic neuropathy of unknown cause). An awareness of the underlying pathological process, and the key distinguishing signs and symptoms, will allow neurologists to identify the glaucomatous process rapidly. Timely referral is essential as glaucoma invariably results in progressive visual loss without treatment. This review therefore condenses the wide field of glaucoma into a practical summary, aimed at practitioners with limited clinical experience of this ophthalmic condition.

Features of ectopic lymphoid-like structures in human uveitis.

Persistent non-infectious uveitis has a significant morbidity, but the extent to which this is accompanied by inflammation driven remodelling of the tissue is unclear. To address this question, we studied a series of samples selected from two ocular tissue repositories and identified 15 samples with focal infiltration. Eleven of fifteen contained lymphocytes, both B cells (CD20 positive) and T cells (CD3 positive). In 20% of the samples there was evidence of ectopic lymphoid like structures with focal aggregations of B cells and T cells, segregated into anatomically different adjacent zones. To investigate inflammation in the tissue, an analysis of 520 immune relevant transcripts was carried out and 24 genes were differentially upregulated, compared with control tissue. Two of these (CD14 and fibronectin) were increased in ocular inflammation compared to control immune tissue (tonsil). We demonstrate that in a significant minority of patients, chronic persistent uveitis leads to dysregulation of ocular immune surveillance, characterized by the development of areas of local ectopic lymphoid like structures, which may be a target for therapeutic intervention directed at antibody producing cells.

Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial.

BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18-55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489). RESULTS: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. CONCLUSION: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.

Micronutrient Deficiencies Presenting with Optic Disc Swelling Associated with or without Intracranial Hypertension: A Systematic Review.

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by optic disc swelling secondary to raised intracranial pressure (ICP) of unknown cause. Obesity is the most established and prevalent risk factor in developed countries. As obesogenic diets are high in calories and nutrient-poor, there may be associated nutritional deficiencies that contribute to the clinical presentation of IIH. Yet none, aside from iron deficiency, are currently included in the inclusion or exclusion criteria for the diagnosis of IIH. Our primary aim was to determine which micronutrient deficiencies, aside from iron deficiency, could present with optic disc swelling associated with or without intracranial hypertension that could potentially meet current IIH diagnostic criteria. To this end, we conducted a systematic search of articles published between 1 January 1980 and 18 December 2020 reporting cases of optic disc swelling associated with micronutrient deficiencies. In total, 65 cases met the eligibility criteria from initial searches: all were case reports and case series with a high risk of bias. Our findings suggest that patients with IIH or unexplained optic disc swelling ought to be screened, investigated, and treated for associated micronutrient deficiencies in vitamin A, B1 and B12; and weight loss interventions in IIH patients ought to promote better nutrition in addition to overall calorie restriction.

Re-programming immunosurveillance in persistent non-infectious ocular inflammation.

Ocular function depends on a high level of anatomical integrity. This is threatened by inflammation, which alters the local tissue over short and long time-scales. Uveitis due to autoimmune disease, especially when it involves the retina, leads to persistent changes in how the eye interacts with the immune system. The normal pattern of immune surveillance, which for immune privileged tissues is limited, is re-programmed. Many cell types, that are not usually present in the eye, become detectable. There are changes in the tissue homeostasis and integrity. In both human disease and mouse models, in the most extreme cases, immunopathological findings consistent with development of ectopic lymphoid-like structures and disrupted angiogenesis accompany severely impaired eye function. Understanding how the ocular environment is shaped by persistent inflammation is crucial to developing novel approaches to treatment.