The Dynamic Oval Pupil

The dynamic oval pupil is defined and its distinction from corectopia, as well as their different clinical significance is proposed. A literature search for instances presenting this condition yielded only 20 such cases with enough clinical data. A review of these cases allows us to draw some tentative conclusions regarding the most likely anatomical location for its causative lesion and the pathophysiological mechanism responsible for its occurrence

Evidence That Pupil Size and Reactivity Are Determined More by Your Parents Than by Your Environment

Purpose: A classic twin study to evaluate the relative contributions of genetic and environmental factors to resting pupil size and reactivity. Methods: Pupillometry was performed on 326 female twins (mean age 64 years) from the TwinsUK Adult Twin Registry, assessing resting pupil diameter in darkness and increasing levels of ambient light, alongside dynamic pupillary characteristics. Maximum-likelihood structural equation models estimated the proportion of trait variance attributable to genetic factors. Results: Mean (SD) pupil diameter in darkness was 5.29 mm (0.81), decreasing to 3.24 mm (0.57) in bright light. Pupil light reaction (PLR) had a mean (SD) amplitude of 1.38 mm (0.27) and latency of 250.34 milliseconds (28.58). Pupil size and PLR were not associated with iris colour, intraocular pressure or refractive error, but were associated with age (diameter beta = -0.02, p = 0.016, constriction amplitude beta = -0.01, p < 0.001, velocity beta = 0.03, p < 0.001, and latency beta = 0.98, p < 0.001). In darkness the resting pupil size showed a MZ intraclass correlation coefficient of 0.85, almost double that of DZ (0.44), suggesting strong additive genetic effects, with the most parsimonious model estimating a heritability of 86% [95% confidence interval (CI) 79-90%] with 14% (95% CI 10-21%) explained by unique environmental factors. PLR amplitude, latency and constriction velocity had estimated heritabilities of 69% (95% CI 54-79%), 40% (95% CI 21-56%), and 64% (95% CI 48-75%), respectively. Conclusion: Genetic effects are key determinants of resting pupil size and reactivity. Future studies to identify these genetic factors could improve our understanding of variation in pupil size and pupillary reactions in health and disease

Automated Pupillometry Using a Prototype Binocular Optical Coherence Tomography System

PURPOSE: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, USA) for pupillometry. DESIGN: Assessment of diagnostic reliability and accuracy. METHODS: Fifty participants with RAPD confirmed using the swinging flashlight method (mean age 49.6 years) and 50 healthy controls (mean age 31.3 years) were examined. Participants twice underwent an automated pupillometry exam using a binocular OCT system that presents a stimulus and simultaneously captures OCT images of the iris-pupil plane of both eyes. Participants underwent a single exam on the RAPDx (Konan Inc, USA), an automated infrared pupillometer. Pupil parameters including maximum and minimum diameter, and anisocoria were measured. The magnitude of RAPD was calculated using the log of the ratio of the constriction amplitude between the eyes. A pathological RAPD was considered to be above ±0.5 log units on both devices. RESULTS: Intraclass correlation coefficient was >0.90 for OCT-derived maximum pupil diameter, minimum pupil diameter, anisocoria. The RAPDx had a sensitivity of 82% and a specificity of 94% for detection of RAPD whereas the binocular OCT had a sensitivity of 74% and specificity of 86%. The diagnostic accuracy of the RAPDx and binocular OCT was 88% (CI: 80-94%) and 80% (CI: 71-87%) respectively. CONCLUSIONS: Binocular OCT-derived pupil parameters had excellent test-retest reliability. Diagnostic accuracy of RAPD was inferior to the RAPDx and is likely related to factors such as eye movement during OCT capture. As OCT becomes ubiquitous, OCT-derived measurements may provide an efficient method of objectively quantifying the pupil responses

Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease. We present a challenging diagnostic and management case of Rosai-Dorfman-Destombes disease in a 48-year-old woman with a relapsing, partially steroid-responsive syndrome comprising patchy, non-length-dependent radiculoneuropathy with diffuse pachymeningitis and widespread systemic disease, and recent dramatic response to novel mitogen-activated kinase pathway inhibition. We discuss the clinical characteristics, diagnosis, recent breakthroughs in pathogenesis and emerging treatment options for Rosai-Dorfman disease and for the histiocytoses with neurological sequelae, including Langerhans cell histiocytosis and Erdheim-Chester disease

Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson's disease

BACKGROUND: Dementia is a common and devastating symptom of Parkinson's disease (PD). Visual function and retinal structure are both emerging as potentially predictive for dementia in Parkinson's but lack longitudinal evidence. METHODS: We prospectively examined higher order vision (skew tolerance and biological motion) and retinal thickness (spectral domain optical coherence tomography) in 100 people with PD and 29 controls, with longitudinal cognitive assessments at baseline, 18 months and 36 months. We examined whether visual and retinal baseline measures predicted longitudinal cognitive scores using linear mixed effects models and whether they predicted onset of dementia, death and frailty using time-to-outcome methods. RESULTS: Patients with PD with poorer baseline visual performance scored lower on a composite cognitive score (β=0.178, SE=0.05, p=0.0005) and showed greater decreases in cognition over time (β=0.024, SE=0.001, p=0.013). Poorer visual performance also predicted greater probability of dementia (χ² (1)=5.2, p=0.022) and poor outcomes (χ² (1) =10.0, p=0.002). Baseline retinal thickness of the ganglion cell-inner plexiform layer did not predict cognitive scores or change in cognition with time in PD (β=-0.013, SE=0.080, p=0.87; β=0.024, SE=0.001, p=0.12). CONCLUSIONS: In our deeply phenotyped longitudinal cohort, visual dysfunction predicted dementia and poor outcomes in PD. Conversely, retinal thickness had less power to predict dementia. This supports mechanistic models for Parkinson's dementia progression with onset in cortical structures and shows potential for visual tests to enable stratification for clinical trials

Extra-ocular muscle MRI in genetically-defined mitochondrial disease

Conventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease

Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson's disease.

BACKGROUND: Dementia is a common and devastating symptom of Parkinson's disease (PD). Visual function and retinal structure are both emerging as potentially predictive for dementia in Parkinson's but lack longitudinal evidence. METHODS: We prospectively examined higher order vision (skew tolerance and biological motion) and retinal thickness (spectral domain optical coherence tomography) in 100 people with PD and 29 controls, with longitudinal cognitive assessments at baseline, 18 months and 36 months. We examined whether visual and retinal baseline measures predicted longitudinal cognitive scores using linear mixed effects models and whether they predicted onset of dementia, death and frailty using time-to-outcome methods. RESULTS: Patients with PD with poorer baseline visual performance scored lower on a composite cognitive score (β=0.178, SE=0.05, p=0.0005) and showed greater decreases in cognition over time (β=0.024, SE=0.001, p=0.013). Poorer visual performance also predicted greater probability of dementia (χ² (1)=5.2, p=0.022) and poor outcomes (χ² (1) =10.0, p=0.002). Baseline retinal thickness of the ganglion cell-inner plexiform layer did not predict cognitive scores or change in cognition with time in PD (β=-0.013, SE=0.080, p=0.87; β=0.024, SE=0.001, p=0.12). CONCLUSIONS: In our deeply phenotyped longitudinal cohort, visual dysfunction predicted dementia and poor outcomes in PD. Conversely, retinal thickness had less power to predict dementia. This supports mechanistic models for Parkinson's dementia progression with onset in cortical structures and shows potential for visual tests to enable stratification for clinical trials

Management of the ataxias : towards best clinical practice

This document aims to provide recommendations for healthcare professionals on the diagnosis and management of people with progressive ataxia. The progressive ataxias are rare neurological conditions, and are often poorly understood by healthcare professionals. Diagnosis has generally been a long process because of the rarity and complexity of the different ataxias1. In addition, many healthcare professionals are unsure how best to manage the conditions and there is sometimes a feeling that little can be done for these patients1,2 Although there are no disease-modifying treatments for the majority of the progressive ataxias, there are many aspects of the conditions that are treatable and it is thus important that this is recognised by the relevant healthcare professionals. The diagnosis and management of the few treatable causes is also of paramount importance. All this highlights the importance of producing these guidelines: in order to increase awareness and understanding of these conditions, and lead to their improved diagnosis and management. With new developments in genetic technologies and the discovery of more genes, diagnosis is improving and has great scope to continue to do so. In addition, research is advancing and many human trials to test medications are taking place, making us more optimistic that disease-modifying treatments will be found for the progressive ataxias

Multimodal Analysis of the Visual Pathways in Friedreich's Ataxia Reveals Novel Biomarkers

Background: Optic neuropathy is a near ubiquitous feature of Friedreich's ataxia (FRDA). Previous studies have examined varying aspects of the anterior and posterior visual pathways but none so far have comprehensively evaluated the heterogeneity of degeneration across different areas of the retina, changes to the macula layers and combined these with volumetric MRI studies of the visual cortex and frataxin level. Methods: We investigated 62 genetically confirmed FRDA patients using an integrated approach as part of an observational cohort study. We included measurement of frataxin protein levels, clinical evaluation of visual and neurological function, optical coherence tomography to determine retinal nerve fibre layer thickness and macular layer volume and volumetric brain MRI. Results: We demonstrate that frataxin level correlates with peripapillary retinal nerve fibre layer thickness and that retinal sectors differ in their degree of degeneration. We also shown that retinal nerve fibre layer is thinner in FRDA patients than controls and that this thinning is influenced by the AAO and GAA1. Furthermore we show that the ganglion cell and inner plexiform layers are affected in FRDA. Our MRI data indicate that there are borderline correlations between retinal layers and areas of the cortex involved in visual processing. Conclusion: Our study demonstrates the uneven distribution of the axonopathy in the retinal nerve fibre layer and highlight the relative sparing of the papillomacular bundle and temporal sectors. We show that thinning of the retinal nerve fibre layer is associated with frataxin levels, supporting the use the two biomarkers in future clinical trials design. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ