{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:05:04Z","timestamp":1780459504197,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Disorders of consciousness (DOC), including vegetative state\/unresponsive wakefulness syndrome (VS\/UWS) and minimally conscious state (MCS), present significant diagnostic challenges. Misdiagnosis rates approach 40%, often due to limitations in detecting subtle behavioural responses through clinical observation alone. Eye-tracking technology offers objective, quantitative assessment of visual behaviours that may reveal covert signs of consciousness. This systematic review aimed to evaluate the diagnostic accuracy of eye-tracking technology compared to the Coma Recovery Scale-Revised (CRS-R) for detecting visual responses and consciousness signs in patients with DOC; to examine stimulus effects; and to assess prognostic value. Methods: A systematic literature search was conducted across SciSpace, Google Scholar, PubMed, and institutional libraries following PRISMA 2020 guidelines. Eligibility criteria specified studies involving patients with prolonged DOC assessed using eye-tracking technology. Data extraction, risk of bias assessment, and GRADE certainty evaluation were conducted systematically. Results: Fifteen studies (n = 4\u2013123 patients; published 2012\u20132025) were included. Eye-tracking detected visual responses in significantly more patients than clinical observation alone (46.2% vs. 18.1% in one study). Mirror stimuli demonstrated the highest detection sensitivity (97% vs. 69% for person and 57% for object). Affectively salient stimuli elicited stronger tracking responses in patients with MCS (37.3% vs. 29.9\u201330.6% neutral). Advanced VR-based systems achieved high diagnostic accuracy (sensitivity 100%, specificity 88.9%) with prognostic value (overt tracking predicting 62.5% command-following at one year). GRADE certainty was Low for detection rates and diagnostic discrimination, and Very Low for sensitivity, specificity, and prognostic outcomes. Conclusions: Eye-tracking provides objective, sensitive assessment of visual behaviours in patients with DOC and may reduce misdiagnosis rates, supporting a conditional recommendation for its use as a supplementary assessment tool alongside CRS-R. Methodological heterogeneity, small sample sizes, and absence of blinding limit certainty. Adequately powered, multicentre prospective studies are urgently needed.<\/jats:p>","DOI":"10.3390\/brainsci16060590","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eye-Tracking Assessment in Patients with Disorders of Consciousness: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-5626","authenticated-orcid":false,"given":"Anna","family":"Estraneo","sequence":"first","affiliation":[{"name":"Fondazione Don Gnocchi, ONLUS, 83054 Sant\u2019Angelo dei Lombardi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Marcello","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Networks Morphology and Systems Biology, Department o f Mental, Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mancino","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via E. Gianturco 113, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"De Feo","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via E. Gianturco 113, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Soricelli","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via E. Gianturco 113, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6490-7694","authenticated-orcid":false,"given":"Monica","family":"Franzese","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via E. Gianturco 113, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cavaliere","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via E. Gianturco 113, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jrm41324","DOI":"10.2340\/jrm.v57.41324","article-title":"Eye tracking to support assessment of patients with prolonged disorder of consciousness\u2014A case series","volume":"57","author":"Johansson","year":"2025","journal-title":"J. Rehabil. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1212\/WNL.58.3.349","article-title":"The minimally conscious state: Definition and diagnostic criteria","volume":"58","author":"Giacino","year":"2002","journal-title":"Neurology"},{"key":"ref_3","first-page":"22","article-title":"Rethinking disorders of consciousness: New research and its implications","volume":"35","author":"Fins","year":"2005","journal-title":"Hastings Cent. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ting, W.K.-C., Perez Velazquez, J.L., and Cusimano, M.D. (2014). Eye Movement Measurement in Diagnostic Assessment of Disorders of Consciousness. Front. Neurol., 5.","DOI":"10.3389\/fneur.2014.00137"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1016\/j.apmr.2004.02.033","article-title":"The JFK Coma Recovery Scale-Revised: Measurement characteristics and diagnostic utility","volume":"85","author":"Giacino","year":"2004","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Schnakers, C., Vanhaudenhuyse, A., Giacino, J., Ventura, M., Boly, M., Majerus, S., Moonen, G., and Laureys, S. (2009). Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment. BMC Neurol., 9.","DOI":"10.1186\/1471-2377-9-35"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0079-6123(05)50028-1","article-title":"Behavioral evaluation of conscious ness in severe brain damage","volume":"150","author":"Majerus","year":"2005","journal-title":"Prog. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1089\/neu.2011.1885","article-title":"Visual pursuit: Within-day variability in the severe disorder of consciousness","volume":"28","author":"Candelieri","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1126\/science.1130197","article-title":"Detecting awareness in the vegetative state","volume":"313","author":"Owen","year":"2006","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s12264-018-0257-z","article-title":"Visual Fixation Assessment in Patients with Disorders of Consciousness Based on Brain-Computer Interface","volume":"34","author":"Xiao","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1177\/0269215514556002","article-title":"A multicentre study of intentional behavioural responses measured using the Coma Recovery Scale-Revised in patients with minimally conscious state","volume":"29","author":"Estraneo","year":"2015","journal-title":"Clin. Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/ene.14151","article-title":"EAN Panel on Coma, Disorders of Consciousness. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness","volume":"27","author":"Kondziella","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00415-011-6114-x","article-title":"From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes","volume":"258","author":"Bruno","year":"2011","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, H.H., Hyun, C., Kang, C.H., Moon, W.J., and Lee, J. (2024). Evaluating impaired consciousness after acquired brain injury using a virtual-reality-based eye-tracking system. Preprint.","DOI":"10.21203\/rs.3.rs-4943480\/v1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zurek, G., Binder, M., Kunka, B., Kosikowski, R., Rodze\u0144, M., Kara\u015b, D., Mucha, G., Olejniczak, R., Gor\u0105czko, A., and Kujawa, K. (2024). Can Eye Tracking Help Assess the State of Consciousness in Non-Verbal Brain Injury Patients?. J. Clin. Med., 13.","DOI":"10.3390\/jcm13206227"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Duchowski, A.T. (2017). Eye Tracking Methodology: Theory and Practice, Springer. [3rd ed.].","DOI":"10.1007\/978-3-319-57883-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22393","DOI":"10.1038\/s41598-021-01858-3","article-title":"Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness","volume":"11","author":"Magliacano","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_18","unstructured":"Holmqvist, K., Nystr\u00f6m, M., Andersson, R., Dewhurst, R., Jarodzka, H., and Van de Weijer, J. (2011). Eye Tracking: A Comprehensive Guide to Methods and Measures, Oxford University Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1007\/s00415-018-8788-9","article-title":"Are visual functions diagnostic signs of the minimally conscious state? an integrative review","volume":"265","author":"Overbeek","year":"2018","journal-title":"J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Slater, M., and Sanchez-Vives, M.V. (2016). Enhancing our lives with immersive virtual reality. Front. Robot. AI, 3.","DOI":"10.3389\/frobt.2016.00074"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wolpaw, J.R., and Wolpaw, E.W. (2012). Brain-Computer Interfaces: Principles and Practice, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780195388855.001.0001"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pfurtscheller, G., Allison, B.Z., Brunner, C., Bauernfeind, G., Solis-Escalante, T., Scherer, R., Zander, T.O., Mueller-Putz, G., Neuper, C., and Birbaumer, N. (2010). The hybrid BCI. Front. Neurosci., 4.","DOI":"10.3389\/fnpro.2010.00003"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"jrm00213","DOI":"10.2340\/16501977-2847","article-title":"Methodological aspects of using a wearable eye-tracker to support diagnostic clinical evaluation of prolonged disorders of consciousness","volume":"53","author":"Johansson","year":"2021","journal-title":"J. Rehabil. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1089\/neu.2023.0188","article-title":"Covert Tracking to Immersive Stimuli in Traumatic Brain Injury Subjects with Disorders of Consciousness","volume":"41","author":"Aklepi","year":"2024","journal-title":"J. Neurotrauma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: An emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1007\/s00415-012-6435-4","article-title":"Quantitative assessment of visual behavior in disorders of consciousness","volume":"259","author":"Trojano","year":"2012","journal-title":"J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s00415-012-6717-x","article-title":"Affective saliency modifies visual tracking behavior in disorders of consciousness","volume":"260","author":"Trojano","year":"2013","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.3109\/02699052.2014.920521","article-title":"Detection of visual pursuit in patients in minimally conscious state: A matter of stimuli and visual plane?","volume":"28","author":"Thonnard","year":"2014","journal-title":"Brain Inj."},{"key":"ref_30","first-page":"159","article-title":"Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients?","volume":"33","author":"Naro","year":"2015","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/ana.24962","article-title":"The repetition of behavioral assessments in diagnosis of disorders of consciousness","volume":"81","author":"Wannez","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1080\/09602011.2017.1310656","article-title":"Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state","volume":"28","author":"Wannez","year":"2018","journal-title":"Neuropsychol. Rehabil."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kujawa, K., Zurek, G., Kwiatkowska, A., Olejniczak, R., and \u017burek, A. (2021). Assessment of Language Functions in Patients with Disorders of Consciousness Using an Alternative Communication Tool. Front Neurol., 12.","DOI":"10.3389\/fneur.2021.684362"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113310","DOI":"10.1016\/j.physbeh.2021.113310","article-title":"Visual fixation in disorders of consciousness: Development of predictive models to support differential diagnosis","volume":"230","author":"Sattin","year":"2021","journal-title":"Physiol. Behav."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kujawa, K., \u017burek, A., Gor\u0105czko, A., Olejniczak, R., and Zurek, G. (2022). Monitoring Eye Movements Depending on the Type of Visual Stimulus in Patients with Impaired Consciousness Due to Brain Damage. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19106280"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1109\/TNSRE.2024.3435016","article-title":"Hybrid brain-computer interface integrating EEG and eye-tracking for consciousness assessment in patients with disorders of consciousness","volume":"32","author":"Yi","year":"2024","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.gaitpost.2019.11.015","article-title":"Age-related changes in gaze sampling strategies during obstacle navigation","volume":"76","author":"Lajoie","year":"2020","journal-title":"Gait Posture"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.visres.2010.10.020","article-title":"Aging and vision","volume":"51","author":"Owsley","year":"2011","journal-title":"Vis. Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/6\/590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:41:10Z","timestamp":1780458070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/6\/590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["brainsci16060590"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16060590","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]}}}