{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:12:59Z","timestamp":1790140379988,"version":"4.0.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have compared the diagnostic ability of different concentrations of 0.125% and 0.0625% dilute pilocarpine for detecting denervation supersensitivity in unilateral Adie\u2019s tonic pupil. This retrospective, observational, case\u2013control study involved 117 subjects, consisting of 56 patients with unilateral Adie\u2019s tonic pupil and 61 controls\u00a0with other causes of unilateral dilated pupils. Subjects underwent the\u00a0dilute pilocarpine test with one of the two concentrations, 0.125% or 0.0625%. Pupillary light reflex was recorded with a dynamic pupillometer at baseline and at 30\u201340\u00a0min after instilling one of the two concentrations of dilute pilocarpine. Diagnostic accuracy of two different concentrations of the dilute pilocarpine test, 0.125% group versus 0.0625% group, were compared by area under the receiver operating characteristic curve (AUC). Diagnostic ability of the dilute pilocarpine test for detecting denervation supersensitivity in unilateral Adie\u2019s tonic pupil was significantly better in the 0.0625% group than in the 0.125% group (AUC\u2009=\u20090.954 vs. 0.840, respectively, <jats:italic>P<\/jats:italic>\u2009=\u20090.047). In the 0.0625% group, the change in maximal pupil diameter of\u2009\u2265\u20090.5\u00a0mm after topical pilocarpine instillation showed 100% sensitivity and 82.8% specificity for detecting Adie\u2019s tonic pupil. This study confirmed that pupillary constriction with 0.0625% pilocarpine is better than 0.125% pilocarpine for detecting denervation supersensitivity in Adie\u2019s tonic pupil. Digital pupillometry is a reliable method for assessing denervation supersensitivity in Adie's tonic pupil.<\/jats:p>","DOI":"10.1038\/s41598-021-89148-w","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:03:45Z","timestamp":1620813825000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Dilute pilocarpine test for diagnosis of Adie\u2019s tonic pupil"],"prefix":"10.1038","volume":"11","author":[{"given":"Yung-Ju","family":"Yoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Min","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Kyung","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"89148_CR1","unstructured":"Walsh, F. B. & Hoyt, W. F. Walsh and Hoyt's Clinical Neuro-Ophthalmology: The Essentials. (Lippincott Williams & Wilkins, 2008)."},{"key":"89148_CR2","doi-asserted-by":"crossref","unstructured":"Boltshauser, E. Clinical Pathways in Neuro-Ophthalmology. (Georg Thieme Verlag KG, 2019).","DOI":"10.1055\/s-0039-1684005"},{"key":"89148_CR3","first-page":"587","volume":"75","author":"HS Thompson","year":"1977","unstructured":"Thompson, H. S. Adie\u2019s syndrome: some new observations. Trans. Am. Ophthalmol. Soc. 75, 587\u2013626 (1977).","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"89148_CR4","unstructured":"Miller, N. R., Walsh, F. B. & Hoyt, W. F. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th edn, (Lippincott Williams & Wilkins, 2005)."},{"key":"89148_CR5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/0002-9394(67)90579-x","volume":"63","author":"IE Loewenfeld","year":"1967","unstructured":"Loewenfeld, I. E. & Thompson, H. S. The tonic pupil: a re-evaluation. Am. J. Ophthalmol. 63, 46\u201387. https:\/\/doi.org\/10.1016\/0002-9394(67)90579-x (1967).","journal-title":"Am. J. Ophthalmol."},{"key":"89148_CR6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/0006-8993(75)90488-6","volume":"100","author":"SJ Bird","year":"1975","unstructured":"Bird, S. J. & Aghajanian, G. K. Denervation supersensitivity in the cholinergic septo-hippocampal pathway: a microiontophoretic study. Brain Res. 100, 355\u2013370. https:\/\/doi.org\/10.1016\/0006-8993(75)90488-6 (1975).","journal-title":"Brain Res."},{"key":"89148_CR7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/0022-510X(86)90070-5","volume":"73","author":"DA Ramsay","year":"1986","unstructured":"Ramsay, D. A. Dilute solutions of phenylephrine and pilocarpine in the diagnosis of disordered autonomic innervation of the iris. Observations in normal subjects, and in the syndromes of Horner and Holmes-Adie. J. Neurol. Sci. 73, 125\u2013134 (1986).","journal-title":"J. Neurol. Sci."},{"key":"89148_CR8","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/0002-9394(75)90753-9","volume":"79","author":"DN Cohen","year":"1975","unstructured":"Cohen, D. N. & Zakov, Z. N. The diagnosis of Adie\u2019s pupil using 0.0625% pilocarpine solution. Am. J. Ophthalmol. 79, 883\u2013885. https:\/\/doi.org\/10.1016\/0002-9394(75)90753-9 (1975).","journal-title":"Am. J. Ophthalmol."},{"key":"89148_CR9","first-page":"295","volume":"11","author":"B Younge","year":"1976","unstructured":"Younge, B. & Buski, Z. Tonic pupil: a simple screening test. Can. J. Ophthalmol. 11, 295\u2013299 (1976).","journal-title":"Can. J. Ophthalmol."},{"key":"89148_CR10","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/s0002-9394(01)01420-9","volume":"133","author":"JA Leavitt","year":"2002","unstructured":"Leavitt, J. A., Wayman, L. L., Hodge, D. O. & Brubaker, R. F. Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil. Am. J. Ophthalmol.. 133, 333\u2013336. https:\/\/doi.org\/10.1016\/s0002-9394(01)01420-9 (2002).","journal-title":"Am. J. Ophthalmol.."},{"key":"89148_CR11","first-page":"171","volume":"18","author":"DM Jacobson","year":"1998","unstructured":"Jacobson, D. M. & Vierkant, R. A. Comparison of cholinergic supersensitivity in third nerve palsy and Adie\u2019s syndrome. J. Neuroophthalmol. 18, 171\u2013175 (1998).","journal-title":"J. Neuroophthalmol."},{"key":"89148_CR12","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.3109\/02713683.2014.980007","volume":"40","author":"LM Cohen","year":"2015","unstructured":"Cohen, L. M., Rosenberg, M. A., Tanna, A. P. & Volpe, N. J. A Novel Computerized portable pupillometer detects and quantifies relative afferent pupillary defects. Curr. Eye Res. 40, 1120\u20131127. https:\/\/doi.org\/10.3109\/02713683.2014.980007 (2015).","journal-title":"Curr. Eye Res."},{"key":"89148_CR13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/WNO.0b013e31823f45e5","volume":"32","author":"A Shwe-Tin","year":"2012","unstructured":"Shwe-Tin, A., Smith, G. T., Checketts, D., Murdoch, I. E. & Taylor, D. Evaluation and calibration of a binocular infrared pupillometer for measuring relative afferent pupillary defect. J. Neuroophthalmol. 32, 111\u2013115. https:\/\/doi.org\/10.1097\/WNO.0b013e31823f45e5 (2012).","journal-title":"J. Neuroophthalmol."},{"key":"89148_CR14","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.3109\/02699052.2015.1045029","volume":"29","author":"P Thiagarajan","year":"2015","unstructured":"Thiagarajan, P. & Ciuffreda, K. J. Pupillary responses to light in chronic non-blast-induced mTBI. Brain Inj. 29, 1420\u20131425. https:\/\/doi.org\/10.3109\/02699052.2015.1045029 (2015).","journal-title":"Brain Inj."},{"key":"89148_CR15","doi-asserted-by":"publisher","first-page":"e0178361","DOI":"10.1371\/journal.pone.0178361","volume":"12","author":"YJ Yoo","year":"2017","unstructured":"Yoo, Y. J., Yang, H. K. & Hwang, J. M. Efficacy of digital pupillometry for diagnosis of Horner syndrome. PLoS ONE 12, e0178361. https:\/\/doi.org\/10.1371\/journal.pone.0178361 (2017).","journal-title":"PLoS ONE"},{"key":"89148_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-56847-4","volume":"10","author":"Y-J Yoo","year":"2020","unstructured":"Yoo, Y. J., Hwang, J. M. & Yang, H. K. Pupillary light reflex in ethambutol-induced optic neuropathy. Sci. Rep. 10, 1\u20136 (2020).","journal-title":"Sci. Rep."},{"key":"89148_CR17","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1212\/wnl.40.5.804","volume":"40","author":"DM Jacobson","year":"1990","unstructured":"Jacobson, D. M. Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders. Neurology 40, 804\u2013808. https:\/\/doi.org\/10.1212\/wnl.40.5.804 (1990).","journal-title":"Neurology"},{"key":"89148_CR18","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/s0161-6420(93)31659-3","volume":"100","author":"DM Jacobson","year":"1993","unstructured":"Jacobson, D. M. & Olson, K. A. Influence of pupil size, anisocoria, and ambient light on pilocarpine miosis. Implications for supersensitivity testing. Ophthalmology 100, 275\u2013280. https:\/\/doi.org\/10.1016\/s0161-6420(93)31659-3 (1993).","journal-title":"Ophthalmology"},{"key":"89148_CR19","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1097\/ICU.0000000000000005","volume":"24","author":"HZ Caglayan","year":"2013","unstructured":"Caglayan, H. Z., Colpak, I. A. & Kansu, T. A diagnostic challenge: dilated pupil. Curr. Opin. Ophthalmol. 24, 550\u2013557. https:\/\/doi.org\/10.1097\/ICU.0000000000000005 (2013).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"89148_CR20","first-page":"218","volume":"15","author":"A Kawasaki","year":"2009","unstructured":"Kawasaki, A. Anisocoria. Lifelong Learn. Neurol. 15, 218\u2013235 (2009).","journal-title":"Lifelong Learn. Neurol."},{"key":"89148_CR21","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/s0161-6420(98)93328-0","volume":"105","author":"RH Kardon","year":"1998","unstructured":"Kardon, R. H., Corbett, J. J. & Thompson, H. S. Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination. Ophthalmology 105, 313\u2013321. https:\/\/doi.org\/10.1016\/s0161-6420(98)93328-0 (1998).","journal-title":"Ophthalmology"},{"key":"89148_CR22","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3980\/J.ISSN.2222-3959.2013.05.20","volume":"6","author":"KM Koh","year":"2013","unstructured":"Koh, K. M. & Kim, U. S. Characteristics of pupillo-accommodative functions according to time of onset, gender and age in tonic pupil. Int. J. Ophthalmol. 6, 659\u2013661. https:\/\/doi.org\/10.3980\/J.ISSN.2222-3959.2013.05.20 (2013).","journal-title":"Int. J. Ophthalmol."},{"key":"89148_CR23","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1097\/01.wno.0000235564.50518.1b","volume":"26","author":"FD Bremner","year":"2006","unstructured":"Bremner, F. D. & Smith, S. E. Pupil abnormalities in selected autonomic neuropathies. J. Neuroophthalmol. 26, 209\u2013219. https:\/\/doi.org\/10.1097\/01.wno.0000235564.50518.1b (2006).","journal-title":"J. Neuroophthalmol."},{"key":"89148_CR24","doi-asserted-by":"publisher","first-page":"14819","DOI":"10.1038\/s41598-018-33202-7","volume":"8","author":"M Quirins","year":"2018","unstructured":"Quirins, M. et al. Conscious processing of auditory regularities induces a pupil dilation. Sci. Rep. 8, 14819. https:\/\/doi.org\/10.1038\/s41598-018-33202-7 (2018).","journal-title":"Sci. Rep."},{"key":"89148_CR25","unstructured":"Team, R. C. R: A Language and Environment for Statistical Computing. https:\/\/www.R-project.org (2019)."},{"key":"89148_CR26","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H Wickham","year":"2016","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2016)."},{"key":"89148_CR27","first-page":"1","volume":"40","author":"H Wickham","year":"2011","unstructured":"Wickham, H. The split-apply-combine strategy for data analysis. J. Stat. Softw. 40, 1\u201329 (2011).","journal-title":"J. Stat. Softw."},{"key":"89148_CR28","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","volume":"12","author":"X Robin","year":"2011","unstructured":"Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 12, 77. https:\/\/doi.org\/10.1186\/1471-2105-12-77 (2011).","journal-title":"BMC Bioinform."},{"key":"89148_CR29","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1177\/1745691611406920","volume":"6","author":"Z Dienes","year":"2011","unstructured":"Dienes, Z. Bayesian versus orthodox statistics: which side are you on?. Perspect. Psychol. Sci. 6, 274\u2013290. https:\/\/doi.org\/10.1177\/1745691611406920 (2011).","journal-title":"Perspect. Psychol. Sci."},{"key":"89148_CR30","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.jmp.2012.08.001","volume":"56","author":"JN Rouder","year":"2012","unstructured":"Rouder, J. N., Morey, R. D., Speckman, P. L. & Province, J. M. Default Bayes factors for ANOVA designs. J. Math. Psychol. 56, 356\u2013374 (2012).","journal-title":"J. Math. Psychol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89148-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89148-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89148-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T08:02:56Z","timestamp":1670054576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89148-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["89148"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-89148-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"29 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10089"}}