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      Efficacy of digital pupillometry for diagnosis of Horner syndrome

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          Abstract

          Objectives

          To evaluate the efficacy of digital pupillometry in the diagnosis of anisocoria related to Horner syndrome in adult patients.

          Design

          Retrospective, observational, case control study.

          Methods

          Nineteen patients with unilateral Horner syndrome (Horner group) and age-matched controls of 30 healthy individuals with normal vision and neither optic nerve dysfunction nor pupillary abnormalities were included. Pupillary light reflex (PLR) of the Horner group and controls were measured by a dynamic pupillometer (PLR-200; NeurOptics Inc., Irvine, USA). Minimal and maximal (min/max) pupil diameters, latency, constriction ratio, constriction velocity, dilation velocity, and total time taken by the pupil to recover 75% of maximal pupil diameter (T75) were noted. PLR were measured at baseline in both groups and at 30–45 minutes later after 0.5% apraclonidine (Iopidine ®; Alcon Laboratories, Fort Worth, TX, USA) instillation in the Horner group.

          Main outcome measures

          The PLR parameters in the affected eye and inter-eye difference before and after 0.5% apraclonidine instillation.

          Results

          In the Horner group, pupil diameters and T75 showed significant difference between the affected eye and unaffected contralateral eye at baseline (all P<0.00625). Compared to controls, inter-eye difference values of pupil diameters and T75 were significantly larger in the Horner group (all P<0.001). After 0.5% apraclonidine instillation, changes in pupil diameter and constriction ratio were significantly larger in the affected eye compared to the unaffected contralateral eye (all P<0.00625). The area under the receiver operating characteristic curves for diagnosing Horner syndrome were largest for baseline inter-eye difference in min/max pupil sizes (AUC = 0.975, 0.994), T75 (AUC = 0.838), and change in min/max pupil sizes after apraclonidine instillation (AUC = 0.923, 0.929, respectively). The diagnostic criteria for Horner syndrome relying on baseline pupillary measurements was defined as one of the two major findings; 1) smaller maximal pupil diameter in the affected eye with an inter-eye difference of > 0.5 mm, or 2) T75 > 2.61 seconds in the affected eye, which showed a sensitivity of 94.7% and specificity of 93.3%. The diagnostic accuracy of apraclonidine testing showed a sensitivity of 84.6% and specificity of 92.3%.

          Conclusions

          Digital pupillometry is an objective method for quantifying PLR. Baseline inter-eye difference in maximal pupil sizes and dilation lag measured by T75 was equally effective in the diagnosis of Horner syndrome compared to the reversal of anisocoria after apraclonidine instillation.

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          Most cited references21

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          • Article: not found

          The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease.

          The pathophysiology of multiple sclerosis is reviewed, with emphasis on the axonal conduction properties underlying the production of symptoms, and the course of the disease. The major cause of the negative symptoms during relapses (e.g. paralysis, blindness and numbness) is conduction block, caused largely by demyelination and inflammation, and possibly by defects in synaptic transmission and putative circulating blocking factors. Recovery from symptoms during remissions is due mainly to the restoration of axonal function, either by remyelination, the resolution of inflammation, or the restoration of conduction to axons which persist in the demyelinated state. Conduction in the latter axons shows a number of deficits, particularly with regard to the conduction of trains of impulses and these contribute to weakness and sensory problems. The mechanisms underlying the sensitivity of symptoms to changes in body temperature (Uhthoff's phenomenon) are discussed. The origin of 'positive' symptoms, such as tingling sensations, are described, including the generation of ectopic trains and bursts of impulses, ephaptic interactions between axons and/or neurons, the triggering of additional, spurious impulses by the transmission of normal impulses, the mechanosensitivity of axons underlying movement-induced sensations (e.g. Lhermitte's phenomenon) and pain. The clinical course of the disease is discussed, together with its relationship to the evolution of lesions as revealed by magnetic resonance imaging and spectroscopy. The earliest detectable event in the development of most new lesions is a breakdown of the blood-brain barrier in association with inflammation. Inflammation resolves after approximately one month, at which time there is an improvement in the symptoms. Demyelination occurs during the inflammatory phase of the lesion. An important mechanism determining persistent neurological deficit is axonal degeneration, although persistent conduction block arising from the failure of repair mechanisms probably also contributes.
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            The measurement and definition of ptosis.

            Measurements of 242 ptotic and normal eyelids were recorded clinically and compared with algebraically derived measurements from projected 35 mm photographs. Accuracy to 1.5 mm or better was obtained in 84% of clinical as compared with photographic measurements. The following definition is suggested: ptosis is present when the upper eyelid is less than 2 mm from midpupil. Reduction of the upper field of vision to 30 degrees or less is present in 97% of eyes with ptosis so defined. Asymmetric ptosis is present in the lower of the two upper eyelids when there is 2 mm or more asymmetry between the levels of the upper eyelids, even if both eyelids are 2 mm or more from midpupil. Although ptosis is best defined in terms of the midpupil to upper lid distance, the diagnosis of ptosis rests with the examining physician based on the clinical evaluation of the patient.
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              Ocular effects of apraclonidine in Horner syndrome.

              To determine the location of action of apraclonidine, an alpha-adrenergic receptor agonist that reduces aqueous production and lowers intraocular pressure (IOP). The study cohort consisted of 6 patients with Horner syndrome (decreased or absent sympathetic innervation of 1 eye). We instilled 1% apraclonidine into the affected eye, and the changes in IOP and pupil diameter (PD) of both eyes were measured over 4 hours. In a separate session, apraclonidine was instilled into the normal eye and the measurements were repeated. The average baseline IOP was 16.3 mm Hg for affected eyes and 16.7 mm Hg for normal eyes. The average maximum ipsilateral reduction in IOP was 5.8 mm Hg in affected eyes and 5.2 mm Hg in normal eyes; this difference was not statistically significant. The average baseline PDs for affected and normal eyes were 3.2 mm and 4.2 mm, respectively. Instillation of apraclonidine into affected eyes produced mydriasis of 1.0 to 4.5 mm; baseline anisocoria reversed in all patients. There was no significant change in the PD of normal eyes after ipsilateral instillation of apraclonidine. Apraclonidine's major site of pharmacologic action for reduction of aqueous production is on postjunctional alpha(2) receptors in the ciliary body. The up-regulation of alpha receptors that occurs with sympathetic denervation unmasks apraclonidine's alpha(1) effect, which clinically causes pupil dilation. Apraclonidine may be a useful medication for the diagnosis of Horner syndrome. Arch Ophthalmol. 2000;118:951-954
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 June 2017
                2017
                : 12
                : 6
                : e0178361
                Affiliations
                [1 ]Department of Ophthalmology, Kangwon National University Hospital, Kangwon National University Graduate School of Medicine, Chuncheon, Korea
                [2 ]Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
                The University of Melbourne, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: HKY JMH.

                • Data curation: HKY JMH.

                • Formal analysis: YJY HKY.

                • Investigation: YJY.

                • Supervision: JMH.

                • Writing – original draft: YJY.

                • Writing – review & editing: HKY JMH.

                ‡ These authors are co-first authors on this work.

                Author information
                http://orcid.org/0000-0003-0837-2864
                Article
                PONE-D-16-41385
                10.1371/journal.pone.0178361
                5456040
                28575101
                1aa866d1-d8ff-43f1-8d32-2f496bd02653
                © 2017 Yoo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 October 2016
                : 11 May 2017
                Page count
                Figures: 3, Tables: 4, Pages: 12
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Head
                Eyes
                Medicine and Health Sciences
                Anatomy
                Head
                Eyes
                Biology and Life Sciences
                Anatomy
                Ocular System
                Eyes
                Medicine and Health Sciences
                Anatomy
                Ocular System
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                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Pupil
                Medicine and Health Sciences
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                Ocular Anatomy
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                Biology and Life Sciences
                Neuroscience
                Reflexes
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                Physical Sciences
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                Electromagnetic Radiation
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                Neuroscience
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                Biology and Life Sciences
                Anatomy
                Integumentary System
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                Eyelids
                Medicine and Health Sciences
                Anatomy
                Integumentary System
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                Custom metadata
                The Institutional Review Board of Seoul National University Bundang Hospital/Ethics commitee has placed ethical restrictions to protect patient identities. However, the data are available to anyone who is interested without restriction. The minimal data set will be available upon request (contact information: SNUBH IRB office, 82-31-787-8804, 98614@ 123456snubh.org .)

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