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Purpose: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, El Segundo, California, USA) for pupillometry., Design: Assessment of diagnostic reliability and accuracy., Methods: Fifty participants with relative afferent pupillary defects (RAPDs) confirmed using the swinging flashlight method (mean age 49.6 years) and 50 healthy control subjects (mean age 31.3 years) were examined. Participants twice underwent an automated pupillometry examination 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 examination on the RAPDx (Konan Medical, Irvine, California, 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 above ±0.5 log units on both devices., Results: The intraclass correlation coefficient was >0.90 for OCT-derived maximum pupil diameter, minimum pupil diameter, and 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% (95% confidence interval 80%-94%) and 80% (95% confidence interval 71%-87%) respectively., Conclusions: Binocular OCT-derived pupil parameters had excellent test-retest reliability. The 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 62-year-old man presented with diplopia, ocular ductional deficits, and sluggish pupils. Pupillometry demonstrated large hyporeactive pupils with no evidence of damage to the sympathetic or parasympathetic innervation, indicating a myopathy of the iris musculature. A single large deletion in mitochondrial DNA and characteristic histochemical features on muscle biopsy suggested a mitochondrial cytopathy. However, ultrastructural examination of skeletal muscle fibers showed tubular aggregates (TAs), a finding not reported in mitochondrial cytopathy. The combination of pupillary abnormalities and TAs suggests that mitochondrial dysfunction may not explain the full extent of abnormalities in this case.

Pupil tests provide a convenient and simple method for evaluation of autonomic function. Most patients with autonomic disorders show evidence of sympathetic or parasympathetic deficits in the pupil, and these can be detected using a combination of clinical signs, pupillometric tests (measuring the responses to light, or an accommodative effort, or a sudden noise) and pharmacological tests (using topically applied drugs both to confirm a deficit and to localize the lesion). Caution is needed in the interpretation of these tests, particularly if the deficits are mixed (i.e. sympathetic and parasympathetic) or bilateral. The pattern of autonomic disturbance in the pupils often correlates poorly with autonomic function elsewhere, but may have diagnostic value in discriminating between different underlying conditions.

Background: Harlequin syndrome is a curious phenomenon in which one half of the face fails to flush during thermal or emotional stress as a result of damage to vasodilator sympathetic fibers. Anecdotal reports suggest that some of these patients have abnormal pupils. In this study we set out to systematically investigate autonomic pupil disturbances in an unselected cohort of patients with harlequin syndrome., Methods: A consecutive series of 39 patients with harlequin syndrome who were referred to a tertiary autonomic function laboratory underwent slit-lamp examinations, testing of deep tendon reflexes, infrared video pupillography and, where needed, additional pharmacologic pupillary testing. Results were compared with a meta-analysis of all previously reported cases of harlequin syndrome (n = 39) identified from a literature search., Results: In 65% of patients, no underlying causative medical disturbance could be identified. In 64% of patients, there were abnormal pupils, most commonly Horner syndrome, which was always present ipsilateral to the side of the face with impaired facial sweating and flushing. The lesion was postganglionic in 9 of 10 patients tested pharmacologically. Five (13%) patients had tonic pupils, most of whom also had tendon areflexia but no other neurologic findings, a pattern consistent with Holmes-Adie syndrome. In 2 of these patients, tonic and Horner pupils coexisted. Normal pupils were present in 36% of patients. These results are similar to those for the 39 previously reported patients with harlequin syndrome., Conclusions: The frequent coexistence of harlequin and Horner syndromes without other neurologic deficits suggests pathologic changes affecting the superior cervical ganglion. Because either syndrome may occur alone, damage is apparently selective. Among the patients with harlequin syndrome who also have tonic pupils and tendon areflexia (Holmes-Adie syndrome), we postulate a ganglionopathy affecting not merely the (sympathetic) superior cervical ganglion, but also the (parasympathetic) ciliary and dorsal root ganglia. Because we found that more than 10% of patients had an undisclosed mass lesion in the chest or neck or a generalized autonomic neuropathy, we recommend a targeted evaluation in selected patients with harlequin syndrome.

Examination of the pupil provides an opportunity to detect disturbances in the autonomic innervation of the eye. The pupil is frequently affected in patients with generalized autonomic neuropathies. This literature review confirms a high prevalence of sympathetic deficits and parasympathetic deficits in acute or subacute dysautonomia, diabetes, amyloidosis, pure autonomic failure, paraneoplastic syndromes, Sjögren syndrome, familial dysautonomia, and dopamine beta-hydroxylase deficiency. It confirms the relative scarcity of a pupil abnormality in patients with multiple system atrophy. There are difficulties in clinical diagnosis of pupil abnormalities and interpretation of pupil pharmacologic tests, particularly when combined sympathetic and parasympathetic deficits are present.