{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:39:14Z","timestamp":1791088754018,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Bayer"},{"name":"Fondation Voir et Entendre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vision"],"abstract":"<jats:p>Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce, requires a good expertise and cannot be used to estimate several PCT parameters, such as the oscillation amplitude or variability. We have developed a computerised setup based on eye-tracking that expands the possibilities of characterising PCT along several dimensions: oscillation frequency and regularity, amplitude and variability, which can be used with a large palette of stimuli (different colours, sizes, shapes or locations), and further allows measuring blinking frequency and eye movements. We used this method to characterise the PCT in young control participants as well as in patients with several pathologies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), Stargardt disease (SD), and Leber hereditary optic neuropathy (LHON). We found that PCT is very regular and stable in young healthy participants, with little inter-individual variability. In contrast, several PCT features are altered in older healthy participants as well as in ocular diseases, including slower dynamics, irregular oscillations, and reduced oscillation amplitude. The distinction between patients and healthy participants based on the calculation of the area under the curve of the receiver operating characteristics (AUC of ROC) were dependent on the pathologies and stimuli (0.7 &lt; AUC &lt; 1). PCT nevertheless provides relevant complementary information to assess the physiopathology of ocular diseases and to probe the functioning of retino-pupillary circuits.<\/jats:p>","DOI":"10.3390\/vision9030051","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the Characteristics of Pupil Cycle Time (PCT) in Neuropathies and Retinopathies"],"prefix":"10.3390","volume":"9","author":[{"given":"Laure","family":"Trinquet","sequence":"first","affiliation":[{"name":"Facult\u00e9 des Sciences M\u00e9dicales et Param\u00e9dicales, Aix-Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzon","family":"Ajasse","sequence":"additional","affiliation":[{"name":"Institut de la Vision, Sorbonne Universit\u00e9, INSERM, CNRS, 75252 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Chavane","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences de la Timone-CNRS UMR 7289, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1430-3649","authenticated-orcid":false,"given":"Richard","family":"Legras","sequence":"additional","affiliation":[{"name":"LuMIn, CNRS, ENS Paris-Saclay, Centrale Supelec, Universit\u00e9 Paris-Saclay, 91190 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-3937","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Matonti","sequence":"additional","affiliation":[{"name":"Centre Monticelli Paradis d\u2019Ophtalmologie, 13008 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Alain","family":"Sahel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0292-8905","authenticated-orcid":false,"given":"Catherine","family":"Vignal-Clermont","sequence":"additional","affiliation":[{"name":"Hopital Fondation, Adolphe de Rothschild 29, Rue Manin, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Lorenceau","sequence":"additional","affiliation":[{"name":"Integrative Neuroscience and Cognition Center, UMR8002, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global Prevalence of Age-Related Macular Degeneration and Disease Burden Projection for 2020 and 2040: A Systematic Review and Meta-Analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, N., Wang, J., Chen, B., Li, Y., and Jiang, B. (2021). Prevalence of Primary Angle Closure Glaucoma in the Last 20 Years: A Meta-Analysis and Systematic Review. Front. Med., 7.","DOI":"10.3389\/fmed.2020.624179"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ajo.2021.06.026","article-title":"False Positive Responses in Standard Automated Perimetry","volume":"233","author":"Heijl","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1167\/iovs.12-10268","article-title":"Factors That Influence Standard Automated Perimetry Test Results in Glaucoma: Test Reliability, Technician Experience, Time of Day, and Season","volume":"53","author":"Wesselink","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","first-page":"1404","article-title":"Variability Components of Standard Automated Perimetry and Frequency-Doubling Technology Perimetry","volume":"42","author":"Spry","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/00041327-200303000-00010","article-title":"Clinical Applications of Pupillography","volume":"23","author":"Wilhelm","year":"2003","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rukmini, A.V., Milea, D., and Gooley, J.J. (2019). Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00076"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kelbsch, C., Strasser, T., Chen, Y., Feigl, B., Gamlin, P.D., Kardon, R., Peters, T., Roecklein, K.A., Steinhauer, S.R., and Szabadi, E. (2019). Standards in Pupillography. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00129"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1073\/pnas.95.1.340","article-title":"Melanopsin: An Opsin in Melanophores, Brain, and Eye","volume":"95","author":"Provencio","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1126\/science.1067262","article-title":"Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock","volume":"295","author":"Berson","year":"2002","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1069609","article-title":"Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity","volume":"295","author":"Hattar","year":"2002","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zele, A.J., and Gamlin, P.D. (2020). Editorial: The Pupil: Behavior, Anatomy, Physiology and Clinical Biomarkers. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00211"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cobeha.2019.06.004","article-title":"Melanopsin Contributions to Non-Visual and Visual Function","volume":"30","author":"Spitschan","year":"2019","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wong, K.Y. (2018). The Roles of Rods, Cones, and Melanopsin in Photoresponses of M4 Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) and Optokinetic Visual Behavior. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00203"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.visres.2006.12.015","article-title":"Human and Macaque Pupil Responses Driven by Melanopsin-Containing Retinal Ganglion Cells","volume":"47","author":"Gamlin","year":"2007","journal-title":"Vis. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.ophtha.2009.02.007","article-title":"Chromatic Pupil Responses","volume":"116","author":"Kardon","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/tvst.8.6.19","article-title":"Objective Measurement of Local Rod and Cone Function Using Gaze-Controlled Chromatic Pupil Campimetry in Healthy Subjects","volume":"8","author":"Kelbsch","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1136\/bjo.28.6.275","article-title":"A Simple Method for the Early Diagnosis of Abnormalities of the Pupillary Reaction","volume":"28","author":"Stern","year":"1944","journal-title":"Br. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/bjo.62.7.495","article-title":"Edge-Light Pupil Cycle Time","volume":"62","author":"Miller","year":"1978","journal-title":"Br. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1136\/bjo.65.11.750","article-title":"The Pupil Cycle Time Test: Age Variations in Normal Subjects","volume":"65","author":"Manor","year":"1981","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4172\/2155-9570.1000517","article-title":"The Assessment of Pupil Cycle Time in Patients with Glaucoma","volume":"7","author":"Karti","year":"2016","journal-title":"J. Clin. Exp. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1136\/jnnp.49.7.771","article-title":"Pupil Cycle Time: A Simple Way of Measuring an Autonomic Reflex","volume":"49","author":"Martyn","year":"1986","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0042-6989(90)90063-Q","article-title":"Evaluation of Pupil Constriction and Dilation from Cycling Measurements","volume":"30","author":"Milton","year":"1990","journal-title":"Vis. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/jcor.jcor_136_23","article-title":"Pupil Cycle Time and Its Significance in Patients with Diabetic Retinopathy","volume":"12","author":"Kalita","year":"2024","journal-title":"J. Clin. Ophthalmol. Res."},{"key":"ref_26","unstructured":"Misra, A., Chaudhury, P., Bedant, S.S., Jena, B., and Sarita, S. (2022). Comparative Study of Pupil Cycle Time with Different Grades of Primary Open-Angle Glaucoma v\/s Normal Study Participants. Int. J. Life Sci., 11."},{"key":"ref_27","unstructured":"Tilmant, C., Charavel, M., Ponrouch, M., Gindre, G., Sarry, L., and Boire, J.-Y. (2003, January 17\u201321). Monitoring and Modeling of Pupillary Dynamics: Study of the Autonomous Nervous System. Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439), Cancun, Mexico."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cortez, M.M., Rae, N., Millsap, L., McKean, N., and Brennan, K.C. (2019). Pupil Cycle Time Distinguishes Migraineurs from Subjects Without Headache. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00478"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s13760-016-0740-0","article-title":"Pupil Cycle Time: As Indicator of Visual Pathway Dysfunction in Multiple Sclerosis","volume":"117","author":"Karahan","year":"2017","journal-title":"Acta Neurol. Belg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lamirel, C., Ajasse, S., Moulignier, A., Salomon, L., Deschamps, R., Gueguen, A., Vignal, C., Cochereau, I., and Lorenceau, J. (2018). A Novel Method of Inducing Endogenous Pupil Oscillations to Detect Patients with Unilateral Optic Neuritis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201730"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3758\/BF03203195","article-title":"A Multipurpose Software Package for Editing Two-Dimensional Animated Images","volume":"22","author":"Lorenceau","year":"1990","journal-title":"Behav. Res. Methods Instrum. Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0278-4327(84)90011-7","article-title":"Chapter 9 Visual Adaptation and Retinal Gain Controls","volume":"3","author":"Shapley","year":"1984","journal-title":"Prog. Retin. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1167\/iovs.10-6538","article-title":"Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease","volume":"52","author":"Chen","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","first-page":"208","article-title":"Color Matches of Patients with Retinitis Pigmentosa","volume":"19","author":"Young","year":"1980","journal-title":"J. Glaucoma"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1167\/iovs.06-0331","article-title":"Male Prevalence of Acquired Color Vision Defects in Asymptomatic Carriers of Leber\u2019s Hereditary Optic Neuropathy","volume":"48","author":"Ventura","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis Pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/bjophthalmol-2016-308823","article-title":"Stargardt Disease: Clinical Features, Molecular Genetics, Animal Models and Therapeutic Options","volume":"101","author":"Tanna","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11940-010-0100-y","article-title":"Leber\u2019s Hereditary Optic Neuropathy","volume":"13","author":"Sadun","year":"2011","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_39","first-page":"181","article-title":"Colour Vision in Stargardt Disease","volume":"54","author":"Vandenbroucke","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ajasse, S., Vignal-Clermont, C., Mohand-Sa\u00efd, S., Coen, C., Romand, C., and Lorenceau, J. (2022). Computerized Biofeedback to Characterize Pupil Cycle Time (PCT) in Neuropathies and Retinopathies. medRxiv.","DOI":"10.1101\/2022.05.24.22275446"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lorenceau, J., Ajasse, S., Barbet, R., Boucart, M., Chavane, F., Lamirel, C., Legras, R., Matonti, F., Rateaux, M., and Rouland, J.-F. (2024). Method to Quickly Map Multifocal Pupillary Response Fields (mPRF) Using Frequency Tagging. Vision, 8.","DOI":"10.3390\/vision8020017"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4103\/0301-4738.81027","article-title":"Pupil Cycle Time and Contrast Sensitivity in Type II Diabetes Mellitus Patients: A Pilot Study","volume":"59","author":"Lee","year":"2011","journal-title":"Indian J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jain, M., Devan, S., Jaisankar, D., Swaminathan, G., Pardhan, S., and Raman, R. (2018). Pupillary Abnormalities with Varying Severity of Diabetic Retinopathy. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-24015-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.2147\/OPTH.S279872","article-title":"Dynamic Pupillometry in Type 2 Diabetes: Pupillary Autonomic Dysfunction and the Severity of Diabetic Retinopathy","volume":"14","author":"Coppell","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Park, J.C., Chen, Y.-F., Blair, N.P., Chau, F.Y., Lim, J.I., Leiderman, Y.I., Shahidi, M., and McAnany, J.J. (2017). Pupillary Responses in Non-Proliferative Diabetic Retinopathy. Sci. Rep., 7.","DOI":"10.1038\/srep44987"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1097\/OPX.0000000000000319","article-title":"Multifocal Pupillography in Early Age-Related Macular Degeneration","volume":"91","author":"Sabeti","year":"2014","journal-title":"Optom. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.9.8.10","article-title":"Chromatic Pupilloperimetry Measures Correlate With Visual Acuity and Visual Field Defects in Retinitis Pigmentosa Patients","volume":"9","author":"Sher","year":"2020","journal-title":"Trans. Vis. Sci. Tech."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1167\/iovs.12-10230","article-title":"Characterization of Pupil Responses to Blue and Red Light Stimuli in Autosomal Dominant Retinitis Pigmentosa Due to NR2E3 Mutation","volume":"53","author":"Kawasaki","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","first-page":"7","article-title":"Comparing Pupil Function with Visual Function in Patients with Leber\u2019s Hereditary Optic Neuropathy","volume":"40","author":"Bremner","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1167\/iovs.03-1230","article-title":"Impairment of the Transient Pupillary Light Reflex in Rpe65\u2212\/\u2212 Mice and Humans with Leber Congenital Amaurosis","volume":"45","author":"Aleman","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1007\/s004170000175","article-title":"The Measurement of Pupil Cycling Time","volume":"238","author":"Howarth","year":"2000","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_52","first-page":"957","article-title":"Comparison of Pupil Perimetry and Visual Perimetry in Normal Eyes: Decibel Sensitivity and Variability","volume":"42","author":"Hong","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","first-page":"1229","article-title":"Pupil Perimetry Using M-Sequence Stimulation Technique","volume":"41","author":"Wilhelm","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Vision"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2411-5150\/9\/3\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:42Z","timestamp":1760032902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2411-5150\/9\/3\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["vision9030051"],"URL":"https:\/\/doi.org\/10.3390\/vision9030051","relation":{},"ISSN":["2411-5150"],"issn-type":[{"value":"2411-5150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}