{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:26:20Z","timestamp":1791894380993,"version":"4.3.4"},"reference-count":217,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye disease (DED) is a highly prevalent multifactorial disorder of the ocular surface that extends beyond local tear film pathology to involve systemic immune, neuroendocrine, and neurosensory mechanisms. Increasing evidence reveals a strong and bidirectional association between DED and psychiatric disorders, particularly depression, anxiety, post-traumatic stress disorder (PTSD), and sleep disturbances. This review synthesises the current knowledge on shared molecular, neuroimmune, and neuropathic pathways that underlie this comorbidity. Key mechanisms include hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysregulation, systemic and ocular inflammation, oxidative stress, mitochondrial dysfunction, and impaired neurotrophic signaling, especially reduced brain-derived neurotrophic factor (BDNF). Dysregulation of monoaminergic neurotransmitters such as serotonin and norepinephrine not only contributes to mood disturbances but also alters tear secretion and corneal pain perception. Corneal nerve changes and trigeminal\u2013limbic sensitisation further reinforce the overlap between neuropathic ocular pain and affective dysregulation. Psychotropic medications, while essential for psychiatric care, may exacerbate ocular surface dysfunction through anticholinergic effects, altered neurotransmission, and tear film instability, highlighting the iatrogenic dimension of this interface. Conversely, tear-based biomarkers, including cytokines, serotonin, and BDNF, offer promising translational tools for patient stratification, diagnosis, and treatment monitoring across ocular and psychiatric domains. Recognising DED as part of a systemic, biopsychosocial continuum is critical for effective management. Multidisciplinary strategies that integrate ophthalmologic and psychiatric care, alongside novel therapies targeting shared molecular pathways, provide a framework for improving outcomes. Future research should prioritise longitudinal studies, biomarker validation, and personalised interventions to address this complex comorbidity.<\/jats:p>","DOI":"10.3390\/ijms262110699","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:18:42Z","timestamp":1762186722000},"page":"10699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Dry Eye Disease and Psychiatric Disorders: Neuroimmune Mechanisms and Therapeutic Perspectives"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3983-1157","authenticated-orcid":false,"given":"Snje\u017eana","family":"Ka\u0161telan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Clinical Hospital Dubrava, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-5361","authenticated-orcid":false,"given":"Lea","family":"Kozina","sequence":"additional","affiliation":[{"name":"Department of Sleep Disorders, University Psychiatric Hospital Vrap\u010de, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-9254","authenticated-orcid":false,"given":"Zora","family":"Tomi\u0107","sequence":"additional","affiliation":[{"name":"Health Centre of the Croatian Department of Internal Affairs, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Bakija","sequence":"additional","affiliation":[{"name":"Department of Integrative Psychiatry, University Psychiatric Hospital \u201cSveti Ivan\u201d, 10090 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomislav","family":"Mateji\u0107","sequence":"additional","affiliation":[{"name":"Surgery Clinic, Clinical Hospital Sveti Duh, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domagoj","family":"Vidovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Sleep Disorders, University Psychiatric Hospital Vrap\u010de, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","first-page":"451","article-title":"TFOS DEWS III: Digest","volume":"279","author":"Stapleton","year":"2025","journal-title":"Arch. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ka\u0161telan, S., Gabri\u0107, K., Mikuli\u010di\u0107, M., Zimak, D.M., Karabati\u0107, M., and Antunica, A.G. (2024). The Influence of Tear Film Quality on Visual Function. Vision, 8.","DOI":"10.3390\/vision8010008"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1007\/s10792-022-02320-7","article-title":"Dry eye syndrome: Comprehensive etiologies and recent clinical trials","volume":"42","author":"Huang","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ka\u0161telan, S., Tomi\u0107, M., Salopek-Rabati\u0107, J., and Novak, B. (2013). Diagnostic Procedures and Management of Dry Eye. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/309723"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"He, Q., Chen, Z., Xie, C., Liu, L., and Wei, R. (2022). The Association Between Dry Eye Disease with Depression, Anxiety and Sleep Disturbance During COVID-19. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.802302"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1177\/11206721211060963","article-title":"Dry eye disease and psychiatric disorders: A systematic review and meta-analysis","volume":"32","author":"Basilious","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/eye.2016.186","article-title":"Depression and anxiety in dry eye disease: A systematic review and meta-analysis","volume":"30","author":"Wan","year":"2016","journal-title":"Eye"},{"key":"ref_8","first-page":"340","article-title":"Depression, Post-traumatic Stress Disorder, and Dry Eye Syndrome: A Study Utilizing the National United States Veterans Affairs Administrative Database","volume":"154","author":"Galor","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"DES143","DOI":"10.1167\/iovs.17-23467","article-title":"Sleep Disorders are a Prevalent and Serious Comorbidity in Dry Eye","volume":"59","author":"Ayaki","year":"2018","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_10","first-page":"377","article-title":"Prevalence and Risk Factors of Dry Eye Syndrome in a United States Veterans Affairs Population","volume":"152","author":"Galor","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1097\/ICO.0000000000002724","article-title":"Association Between Dry Eye Disease and Newly Diagnosed Obsessive-Compulsive Disorder","volume":"40","author":"Eroglu","year":"2021","journal-title":"Cornea"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.2147\/OPTH.S89700","article-title":"Associations between signs and symptoms of dry eye disease: A systematic review","volume":"9","author":"Bartlett","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1136\/bjophthalmol-2017-310633","article-title":"Epidemiology of discordance between symptoms and signs of dry eye","volume":"102","author":"Ong","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1097\/ICO.0000000000001932","article-title":"The Correlation Between Dry Eyes, Anxiety and Depression: The Sicca, Anxiety and Depression Study","volume":"38","author":"Bitar","year":"2019","journal-title":"Cornea"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e005296","DOI":"10.1136\/bmjopen-2014-005296","article-title":"Discrepancy between subjectively reported symptoms and objectively measured clinical findings in dry eye: A population based analysis","volume":"4","author":"Hua","year":"2014","journal-title":"BMJ Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/tvst.7.6.35","article-title":"The Relationship of Dry Eye Disease with Depression and Anxiety: A Naturalistic Observational Study","volume":"7","author":"Kitazawa","year":"2018","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e001584","DOI":"10.1136\/bmjophth-2023-001584","article-title":"Associations between dry eye disease and sleep quality: A cross-sectional analysis","volume":"9","author":"Ayoubi","year":"2024","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kim, M., Chun, Y.S., and Kim, K.W. (2022). Different perception of dry eye symptoms between patients with and without primary Sjogren\u2019s syndrome. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-06191-x"},{"key":"ref_19","first-page":"e51447","article-title":"Subjective Dry Eye Symptoms and Objective Ocular Surface Signs in a Civil Air Crew Population: A Cross-Sectional Study","volume":"16","author":"Fachinetti","year":"2024","journal-title":"Cureus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2147\/CIA.S137580","article-title":"Association of dry eye disease with psychiatric or neurological disorders in elderly patients","volume":"ume 12","author":"Han","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1136\/annrheumdis-2016-210283","article-title":"Discordance between tender and swollen joint count as well as patient\u2019s and evaluator\u2019s global assessment may reduce likelihood of remission in patients with rheumatoid arthritis and psoriatic arthritis: Data from the prospective multicentre NOR-DMARD study","volume":"76","author":"Michelsen","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yu, H., Zeng, W., Xu, M., Wu, W., and Feng, Y. (2022). Experience of Dry Eye Patients with Anxiety and Depression: A Qualitative Study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.830986"},{"key":"ref_23","first-page":"588","article-title":"Mental Disorders as Influencing Factors for Discordances in the Signs and Symptoms of Dry Eye Disease","volume":"33","author":"Bakija","year":"2021","journal-title":"Psychiatr Danub."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1080\/26895293.2022.2120091","article-title":"The central symptoms of depression, anxiety, and somatization: A network analysis","volume":"15","author":"Ma","year":"2022","journal-title":"All Life"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113261","DOI":"10.1016\/j.socscimed.2020.113261","article-title":"Psychological resilience, depression, anxiety, and somatization symptoms in response to COVID-19: A study of the general population in China at the peak of its epidemic","volume":"262","author":"Ran","year":"2020","journal-title":"Soc. Sci. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s10792-024-03133-6","article-title":"An important contributing factor in dry eye disease: Somatization","volume":"44","author":"Yavrum","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.optom.2020.10.002","article-title":"Why the symptoms and objective signs of dry eye disease may not correlate","volume":"14","author":"McMonnies","year":"2021","journal-title":"J. Optom."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hassamal, S. (2023). Chronic stress, neuroinflammation, and depression: An overview of pathophysiological mechanisms and emerging anti-inflammatories. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1130989"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.ophtha.2015.04.010","article-title":"Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye","volume":"122","author":"Chhadva","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1167\/iovs.06-0127","article-title":"Relation between Corneal Innervation with Confocal Microscopy and Corneal Sensitivity with Noncontact Esthesiometry in Patients with Dry Eye","volume":"48","author":"Acosta","year":"2007","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1167\/tvst.10.6.26","article-title":"Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation with Clinical Parameters","volume":"10","author":"Ma","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jtos.2021.08.004","article-title":"Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study","volume":"22","author":"Cox","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jastrz\u0119bska-Miazga, I., Machna, B., Wygl\u0119dowska-Promie\u0144ska, D., and Sm\u0119dowski, A. (2025). The Role of Substance P in Corneal Homeostasis. Biomolecules, 15.","DOI":"10.3390\/biom15050729"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2451194","DOI":"10.1080\/07853890.2025.2451194","article-title":"Tear neuropeptides are associated with clinical symptoms and signs of dry eye patients","volume":"57","author":"Zhang","year":"2025","journal-title":"Ann. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aleixandre-Carrera, F., Engelmayer, N., Ares-Su\u00e1rez, D., Acosta, M.d.C., Belmonte, C., Gallar, J., Meseguer, V., and Binshtok, A.M. (2021). Optical Assessment of Nociceptive TRP Channel Function at the Peripheral Nerve Terminal. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020481"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"He, Q., Chen, Z., Xie, C., Liu, L., Yang, H., and Wei, R. (2022). Relationship Between Dry Eye Disease and Emotional Disorder: The Mediating Effect of Health Anxiety. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.771554"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, H., Han, X., Guo, L., Ceban, F., Liao, Y., Shi, J., Wang, W., Liu, Y., and Song, W. (2023). Predictive potential of somatic symptoms for the identification of subthreshold depression and major depressive disorder in primary care settings. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.999047"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/jamaophthalmol.2022.0140","article-title":"Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study","volume":"140","author":"Zhou","year":"2022","journal-title":"JAMA Ophthalmol."},{"key":"ref_39","first-page":"596","article-title":"Comparison of the Schein and Osdi Questionnaire as Indicator of Tear Film Stability in Patients with Schizophrenia","volume":"33","author":"Bakija","year":"2021","journal-title":"Psychiatr Danub."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Takeuchi, T., Hashimoto, K., Koyama, A., Asakura, K., and Hashizume, M. (2024). The Association of Central Sensitisation with Depression, Anxiety, and Somatic Symptoms: A Cross-Sectional Study of a Mental Health Outpatient Clinic in Japan. Life, 14.","DOI":"10.3390\/life14050612"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jtos.2025.03.005","article-title":"The association between personality and dry eye disease: A large cross-sectional study","volume":"37","author":"Magno","year":"2025","journal-title":"Ocul. Surf."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Toth, M., Joki\u0107-Begi\u0107, N., and Kra\u0161i\u0107, S. (2025). The Relationship Between Anxiety Sensitivity, Emotional States, and Dry Eye Disease Symptom Severity: A Cross-Sectional Study. Vision, 9.","DOI":"10.3390\/vision9020036"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1038\/eye.2010.67","article-title":"Impact of symptomatic dry eye on vision-related daily activities: The Singapore Malay Eye Study","volume":"24","author":"Tong","year":"2010","journal-title":"Eye"},{"key":"ref_44","first-page":"S580","article-title":"Psychiatric Disorders and Dry Eye Disease\u2014A Transdisciplinary Approach","volume":"33","author":"Kastelan","year":"2021","journal-title":"Psychiatr Danub."},{"key":"ref_45","first-page":"470","article-title":"The Association Between Dry Eye Disease and Depression and Anxiety in a Large Population-Based Study","volume":"159","author":"Weaver","year":"2015","journal-title":"Arch. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Liang, C.-Y., Cheang, W.-M., Wang, C.-Y., Lin, K.-H., Wei, L.-C., Chen, Y.-Y., and Shen, Y.-C. (2020). The association of dry eye syndrome and psychiatric disorders: A nationwide population-based cohort study. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-020-01395-z"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.sleep.2015.06.021","article-title":"The association between sleep duration and dry eye syndrome among Korean adults","volume":"16","author":"Lee","year":"2015","journal-title":"Sleep. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3109\/02713683.2015.1056804","article-title":"Dry eye-related visual blurring and irritative symptoms and their association with depression and anxiety in eye clinic patients","volume":"41","author":"Liyue","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jtos.2020.04.005","article-title":"Prevalence and risk factors of dry eye in 79,866 participants of the population-based Lifelines cohort study in the Netherlands","volume":"19","author":"Vehof","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/j.2040-4603.2016.tb00694.x","article-title":"Regulation of the hypothalamic-pituitary-adrenocortical stress response","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lei, A.A., Phang, V.W.X., Lee, Y.Z., Kow, A.S.F., Tham, C.L., Ho, Y.-C., and Lee, M.T. (2025). Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus\u2014A Mini Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26072940"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101588","DOI":"10.1016\/j.smrv.2022.101588","article-title":"HPA axis activity in patients with chronic insomnia: A systematic review and meta-analysis of case\u2013control studies","volume":"62","author":"Dressle","year":"2022","journal-title":"Sleep Med. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bertollo, A.G., Santos, C.F., Bagatini, M.D., and Ign\u00e1cio, Z.M. (2025). Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1541075"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/s41380-019-0501-6","article-title":"Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: The role of cognitive-affective and somatic symptoms","volume":"25","author":"Iob","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1001\/jamaophthalmol.2016.3642","article-title":"Assessment of Somatosensory Function in Patients with Idiopathic Dry Eye Symptoms","volume":"134","author":"Galor","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hyon, J.Y., Yang, H.K., and Han, S.B. (2019). Association between Dry Eye Disease and Psychological Stress among Paramedical Workers in Korea. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40539-0"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Glavina, A., Zurak, P., Martinovi\u0107, D., Gotovac, M., \u0160upe-Domi\u0107, D., and Lugovi\u0107-Mihi\u0107, L. (2024). Evaluation of the Hypothalamic\u2013Pituitary\u2013Adrenal Axis in Patients with Primary Sj\u00f6gren\u2019s Disease. Medicina, 60.","DOI":"10.3390\/medicina60111886"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.2147\/JMDH.S488956","article-title":"Association Between Dry Eye Disease with Anxiety and Depression Among Medical Sciences Students in Qassim Region: Cortisol Levels in Tears as a Stress Biomarker","volume":"17","author":"Alkozi","year":"2024","journal-title":"J. Multidiscip. Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1210\/jc.2009-0555","article-title":"Self-Reported Sleep Duration and Sleep Disturbance Are Independently Associated with Cortisol Secretion in the Whitehall II Study","volume":"94","author":"Kumari","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/s41380-022-01806-1","article-title":"Molecular pathways of major depressive disorder converge on the synapse","volume":"28","author":"Fries","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.pnpbp.2003.11.018","article-title":"Central monoamines and their role in major depression","volume":"28","author":"Elhwuegi","year":"2004","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hao, S., Shi, W., Liu, W., Chen, Q.-Y., and Zhuo, M. (2023). Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety. Front. Synaptic Neurosci., 15.","DOI":"10.3389\/fnsyn.2023.1122381"},{"key":"ref_63","unstructured":"International Classification of Disease (ICD), 11th Edition (2025, August 25). Depressive Disorders. Available online: https:\/\/icd.who.int\/browse\/2025-01\/mms\/en#578635574."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4306\/pi.2015.12.1.1","article-title":"Pain and Depression: A Neurobiological Perspective of Their Relationship","volume":"12","author":"Han","year":"2015","journal-title":"Psychiatry Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1080\/14656566.2019.1647166","article-title":"Treatment of central sensitization in patients with chronic pain: Time for change?","volume":"20","author":"Nijs","year":"2019","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_66","first-page":"e35331","article-title":"Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain","volume":"15","author":"Ohashi","year":"2023","journal-title":"Cureus"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e81436","DOI":"10.7554\/eLife.81436","article-title":"Evidence for dopaminergic involvement in endogenous modulation of pain relief","volume":"12","author":"Desch","year":"2023","journal-title":"eLife"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11427-014-4638-x","article-title":"Emotional regulation of pain: The role of noradrenaline in the amygdala","volume":"57","author":"Strobel","year":"2014","journal-title":"Sci. China Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jpain.2015.10.019","article-title":"Neuropathic Ocular Pain due to Dry Eye Is Associated with Multiple Comorbid Chronic Pain Syndromes","volume":"17","author":"Galor","year":"2016","journal-title":"J. Pain."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hole, C., Dhamsania, A., Brown, C., and Ryznar, R. (2025). Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment. Cells, 14.","DOI":"10.3390\/cells14080607"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Saggu, S., Pless, A., Dew, E., Ware, D., Jiao, K., and Wang, Q. (2025). Monoamine signaling and neuroinflammation: Mechanistic connections and implications for neuropsychiatric disorders. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1543730"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.advms.2017.03.003","article-title":"Pro-inflammatory cytokines associated with clinical severity of dry eye disease of patients with depression","volume":"62","author":"Mrugacz","year":"2017","journal-title":"Adv. Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yang, H., Tian, Q., Luan, L., Yang, M., Li, C., and Zhang, X. (2025). NGF-\u03b2 and BDNF levels are altered in male patients with chronic schizophrenia: Effects on clinical symptoms. BMC Psychiatry, 25.","DOI":"10.1186\/s12888-025-06685-8"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s12017-025-08857-x","article-title":"Unlocking Alzheimer\u2019s Disease: The Role of BDNF Signaling in Neuropathology and Treatment","volume":"27","author":"Alqahtani","year":"2025","journal-title":"Neuromolecular Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yu, Z., Joy, S., Mi, T., Yazdanpanah, G., Burgess, K., and de Paiva, C.S. (2022). New, potent, small molecule agonists of tyrosine kinase receptors attenuate dry eye disease. Front. Med., 9.","DOI":"10.3389\/fmed.2022.937142"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Sano, K., Kawashima, M., Imada, T., Suzuki, T., Nakamura, S., Mimura, M., Tanaka, K.F., and Tsubota, K. (2019). Enriched environment alleviates stress-induced dry-eye through the BDNF axis. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-39467-w"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1177\/11206721251335060","article-title":"Implementing potential biomarkers for early detection of retinal changes in Parkinson\u2019s disease: Preliminary study on BDNF role","volume":"35","author":"Malvasi","year":"2025","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5990","DOI":"10.1167\/iovs.15-17036","article-title":"Single Nucleotide Polymorphisms in the BDNF, VDR, and DNASE 1 Genes in Dry Eye Disease Patients: A Case-Control Study","volume":"56","author":"Hallak","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/mr\/roae071","article-title":"A study on factors related to sleep disorders and serum BDNF expression levels in patients with primary Sj\u00f6gren\u2019s syndrome","volume":"35","author":"Han","year":"2024","journal-title":"Mod. Rheumatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1007\/s00213-022-06250-1","article-title":"Rapid antidepressant-like effects of muscarinic receptor antagonists require BDNF-dependent signaling in the ventrolateral periaqueductal gray","volume":"239","author":"Kan","year":"2022","journal-title":"Psychopharmacology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"149925","DOI":"10.1016\/j.brainres.2025.149925","article-title":"Neuroprotective effects of Lactiplantibacillus plantarum and Pediococcus pentosaceus strains against oxidative stress via modulation of Nrf2-mediated antioxidation and anti-apoptosis","volume":"1866","author":"Lee","year":"2025","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tayeb, A.E.K.A., Poinsignon, V., Chappell, K., Bouligand, J., Becquemont, L., and Verstuyft, C. (2023). Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages. Antioxidants, 12.","DOI":"10.3390\/antiox12040942"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.psyneuen.2014.09.025","article-title":"Is depression associated with increased oxidative stress? A systematic review and meta-analysis","volume":"51","author":"Black","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/PSY.0000000000000009","article-title":"Depression and Oxidative Stress","volume":"76","author":"Palta","year":"2014","journal-title":"Psychosom. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Fu, Q., Qiu, R., Liang, J., Wu, S., Huang, D., Qin, Y., Li, Q., Shi, X., Xiong, X., and Jiang, Z. (2025). Sugemule-7 alleviates oxidative stress, neuroinflammation, and cell death, promoting synaptic plasticity recovery in mice with postpartum depression. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-85276-9"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/bcb-2024-0237","article-title":"Multifaceted roles of MeCP2 in cellular regulation and phase separation: Implications for neurodevelopmental disorders, depression, and oxidative stress","volume":"103","author":"Good","year":"2025","journal-title":"Biochem. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.3892\/mmr.2015.4104","article-title":"MeCP2 controls hippocampal brain-derived neurotrophic factor expression via homeostatic interactions with microRNA-132 in rats with depression","volume":"12","author":"Su","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/aos.14892","article-title":"Oxidative and antioxidative stress markers in dry eye disease: A systematic review and meta-analysis","volume":"100","author":"Navel","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bu, J., Liu, Y., Zhang, R., Lin, S., Zhuang, J., Sun, L., Zhang, L., He, H., Zong, R., and Wu, Y. (2024). Potential New Target for Dry Eye Disease\u2014Oxidative Stress. Antioxidants, 13.","DOI":"10.3390\/antiox13040422"},{"key":"ref_91","first-page":"1","article-title":"Review of the Role of Oxidative Stress in Ocular Surface Disease and Use of MDA and 4-HNE in Tears as Potential Markers","volume":"2","author":"Simpson","year":"2022","journal-title":"J. Ophthalmic Res. Vis. Care"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/ame2.70000","article-title":"Astaxanthin ameliorates benzalkonium chloride\u2013induced dry eye disease through suppressing inflammation and oxidative stress via Keap1-Nrf2\/HO-1 signaling pathways","volume":"8","author":"Liu","year":"2025","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"177311","DOI":"10.1016\/j.ejphar.2025.177311","article-title":"Exploring the effect of chlorogenic acid on oxidative stress and autophagy in dry eye mice via the AMPK\/ULK1 pathway","volume":"991","author":"Chen","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Arslan, M.A., Rousseau, A., Liang, H., Chardonnet, S., Pionneau, C., Rabut, G., Le Goazigo, A.R., Labetoulle, M., Baudouin, C., and Brignole-Baudouin, F. (2025). Deficiency of antioxidant enzyme PRDX6 and mucosal chemokine CXCL17: Unraveling the factors behind oxidative stress and mucosal homeostasis disruption in dry eye disease. Biochim. Et Biophys. Acta-Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2025.167911"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41420-024-02159-0","article-title":"Multifaceted mitochondrial as a novel therapeutic target in dry eye: Insights and interventions","volume":"10","author":"Ouyang","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2023.11.021","article-title":"Mitochondria-targeted SkQ1 nanoparticles for dry eye disease: Inhibiting NLRP3 inflammasome activation by preventing mitochondrial DNA oxidation","volume":"365","author":"Huang","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_97","first-page":"013444","article-title":"Ameliorative Potential of Resveratrol in Dry Eye Disease by Restoring Mitochondrial Function","volume":"2022","author":"Chen","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1167\/iovs.65.4.33","article-title":"Mitochondrial DNA-Activated cGAS-STING Signaling in Environmental Dry Eye","volume":"65","author":"Tan","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Allen, J., Romay-Tallon, R., Brymer, K.J., Caruncho, H.J., and Kalynchuk, L.E. (2018). Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00386"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Li, W., Zhu, L., Chen, Y., Zhuo, Y., Wan, S., and Guo, R. (2023). Association between mitochondrial DNA levels and depression: A systematic review and meta-analysis. BMC Psychiatry, 23.","DOI":"10.1186\/s12888-023-05358-8"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41398-023-02518-y","article-title":"Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression","volume":"13","author":"Liu","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41398-021-01723-x","article-title":"Blood-based mitochondrial respiratory chain function in major depression","volume":"11","author":"Mellon","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Casaril, A.M., Dantzer, R., and Bas-Orth, C. (2021). Neuronal Mitochondrial Dysfunction and Bioenergetic Failure in Inflammation-Associated Depression. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.725547"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S1569-7339(10)70090-4","article-title":"Serotonin in Mood and Emotion","volume":"21","author":"Hensler","year":"2010","journal-title":"Handb. Behav. Neurosci."},{"key":"ref_105","unstructured":"Bamalan, O.A., Moore, M.J., and Al Khalili, Y. (2025, June 19). Physiology, Serotonin, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK545168\/."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41380-024-02459-y","article-title":"The involvement of serotonin in major depression: Nescience in disguise?","volume":"29","author":"Arnone","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Lin, J., Liu, W., Guan, J., Cui, J., Shi, R., Wang, L., Chen, D., and Liu, Y. (2023). Latest updates on the serotonergic system in depression and anxiety. Front. Synaptic Neurosci., 15.","DOI":"10.3389\/fnsyn.2023.1124112"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1038\/s41380-022-01661-0","article-title":"The serotonin theory of depression: A systematic umbrella review of the evidence","volume":"28","author":"Moncrieff","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","article-title":"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions","volume":"22","author":"Howard","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.3758\/s13415-023-01116-1","article-title":"Serotonin and emotion regulation: The impact of tryptophan depletion on emotional experience, neural and autonomic activity","volume":"23","author":"Iacob","year":"2023","journal-title":"Cogn. Affect. Behav. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Park, I., Choi, M., Kim, J., Jang, S., Kim, D., Kim, J., Choe, Y., Geum, D., Yu, S.-W., and Choi, J.-W. (2024). Role of the circadian nuclear receptor REV-ERB\u03b1 in dorsal raphe serotonin synthesis in mood regulation. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06647-y"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Liu, H.N., Nakamura, M., and Kawashima, H. (2024). New Role of the Serotonin as a Biomarker of Gut\u2013Brain Interaction. Life, 14.","DOI":"10.20944\/preprints202408.1730.v1"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Imada, T., Nakamura, S., Hisamura, R., Izuta, Y., Jin, K., Ito, M., Kitamura, N., Tanaka, K.F., Mimura, M., and Shibuya, I. (2017). Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06022-4"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1569-2590(05)10002-0","article-title":"Tears and their secretion","volume":"10","author":"Dartt","year":"2005","journal-title":"Adv. Organ Biol."},{"key":"ref_115","first-page":"1040","article-title":"Serotonin receptor subtype mRNA expression in human ocular tissues, determined by RT-PCR","volume":"12","author":"Sharif","year":"2006","journal-title":"Mol Vis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.1167\/iovs.02-1292","article-title":"Pharmacological Characterization of a Serotonin Receptor (5-HT7) Stimulating cAMP Production in Human Corneal Epithelial Cells","volume":"44","author":"Crider","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"52","DOI":"10.32607\/actanaturae.10906","article-title":"Molecular Mechanisms and Clinical Manifestations of Catecholamine Dysfunction in the Eye in Parkinson\u2019s Disease as a Basis for Developing Early Diagnosis","volume":"12","author":"Pavlenko","year":"2020","journal-title":"Acta Naturae"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Zhou, X., Dai, Y., Zhai, Z., and Hong, J. (2021). WAY-100635 Alleviates Corneal Lesions Through 5-HT1A Receptor-ROS-Autophagy Axis in Dry Eye. Front. Med., 8.","DOI":"10.3389\/fmed.2021.799949"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.280.2.147","article-title":"Persistent Pain and Well-being","volume":"280","author":"Gureje","year":"1998","journal-title":"JAMA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jpain.2016.01.474","article-title":"Pain Sensitivity in Patients with Major Depression: Differential Effect of Pain Sensitivity Measures, Somatic Cofactors, and Disease Characteristics","volume":"17","author":"Hermesdorf","year":"2016","journal-title":"J. Pain."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Machali\u0144ska, A., Kuligowska, A., Ziontkowska-Wrza\u0142ek, A., Stroynowska, B., Pius-Sadowska, E., Safranow, K., Machali\u0144ski, J., Mozolewska-Piotrowska, K., and Machali\u0144ski, B. (2024). The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116072"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Tanase, D.M., Valasciuc, E., Gosav, E.M., Floria, M., Buliga-Finis, O.N., Ouatu, A., Cucu, A.I., Botoc, T., and Costea, C.F. (2025). Enhancing Retinal Resilience: The Neuroprotective Promise of BDNF in Diabetic Retinopathy. Life, 15.","DOI":"10.3390\/life15020263"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"122996","DOI":"10.1016\/j.lfs.2024.122996","article-title":"Visual stimulation and brain-derived neurotrophic factor (BDNF) have protective effects in experimental autoimmune uveoretinitis","volume":"355","author":"Zloh","year":"2024","journal-title":"Life Sci."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Nagino, K., Sung, J., Oyama, G., Hayano, M., Hattori, N., Okumura, Y., Fujio, K., Akasaki, Y., Huang, T., and Midorikawa-Inomata, A. (2022). Prevalence and characteristics of dry eye disease in Parkinson\u2019s disease: A systematic review and meta-analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22037-y"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Davinelli, S., Medoro, A., Siracusano, M., Savino, R., Saso, L., Scapagnini, G., and Mazzone, L. (2025). Oxidative stress response and NRF2 signaling pathway in autism spectrum disorder. Redox Biol., 83.","DOI":"10.1016\/j.redox.2025.103661"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Guerrero-Moreno, A., Liang, H., Moreau, N., Luzu, J., Rabut, G., Parsadaniantz, S.M., Labb\u00e9, A., Baudouin, C., and Goazigo, A.R.-L. (2021). Corneal Nerve Abnormalities in Painful Dry Eye Disease Patients. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101424"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Bucsan, R., Coroleuc\u0103, R., Garh\u00f6fer, G., Popa-Cherecheanu, A., Schmetterer, L., and Iancu, R. (2024). Confocal Microscopy of the Cornea in Aqueous-Deficient Dry Eye Disease\u2014A Literature Review. Diagnostics, 14.","DOI":"10.3390\/diagnostics14151613"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/opo.13186","article-title":"The impact of dry eye disease on corneal nerve parameters: A systematic review and meta-analysis","volume":"43","author":"Chiang","year":"2023","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/jns.12514","article-title":"Anxiety and depression in small fiber neuropathy","volume":"27","author":"Damci","year":"2022","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1900\/RDS.2020.16.35","article-title":"Depression Symptoms in Patients with Diabetic Peripheral Neuropathy","volume":"16","author":"Alghafri","year":"2020","journal-title":"Rev. Diabet. Stud."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"100964","DOI":"10.1016\/j.bbih.2025.100964","article-title":"How does chronic psychosocial distress induce pain? Focus on neuroinflammation and neuroplasticity changes","volume":"47","author":"Helyes","year":"2025","journal-title":"Brain Behav. Immun.-Health"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9724371","DOI":"10.1155\/2017\/9724371","article-title":"The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain","volume":"2017","author":"Sheng","year":"2017","journal-title":"Neural Plast."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Barcelon, E.E., Cho, W.-H., Jun, S.B., and Lee, S.J. (2019). Brain Microglial Activation in Chronic Pain-Associated Affective Disorder. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00213"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Tsai, C.-Y., Jiesisibieke, Z.L., and Tung, T.-H. (2022). Association between dry eye disease and depression: An umbrella review. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.910608"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jneuroim.2016.05.003","article-title":"Calcitonin gene-related peptide contributes to peripheral nerve injury-induced mechanical hypersensitivity through CCL5 and p38 pathways","volume":"297","author":"Malon","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/j.pain.0000000000000831","article-title":"The role of calcitonin gene\u2013related peptide in peripheral and central pain mechanisms including migraine","volume":"158","author":"Iyengar","year":"2017","journal-title":"PAIN\u00ae"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin Gene-Related Peptide: Physiology and Pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Hashikawa-Hobara, N., Ogawa, T., Sakamoto, Y., Matsuo, Y., Ogawa, M., Zamami, Y., and Hashikawa, N. (2015). Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice. Sci. Rep., 5.","DOI":"10.1038\/srep12559"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e16106","DOI":"10.1111\/ene.16106","article-title":"Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine","volume":"31","author":"Lentsch","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1167\/iovs.65.4.30","article-title":"CGRP Released by Corneal Sensory Nerve Maintains Tear Secretion of the Lacrimal Gland","volume":"65","author":"Ma","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1038\/s41467-019-13536-0","article-title":"TRPV1 activity and substance P release are required for corneal cold nociception","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12974-021-02162-7","article-title":"Capsazepine decreases corneal pain syndrome in severe dry eye disease","volume":"18","author":"Fakih","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Meza, R.C., Ancat\u00e9n-Gonz\u00e1lez, C., Chiu, C.Q., and Ch\u00e1vez, A.E. (2022). Transient Receptor Potential Vanilloid 1 Function at Central Synapses in Health and Disease. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.864828"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Chahl, L.A. (2024). TRPV1 Channels in the Central Nervous System as Drug Targets. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060756"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.bbi.2024.10.028","article-title":"Chemogenetic targeting TRPV1 in obesity-induced depression: Unveiling therapeutic potential of eicosapentaenoic acid and acupuncture","volume":"123","author":"Lin","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1756-6606-7-27","article-title":"No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex","volume":"7","author":"Liu","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Won, E., Kang, J., Choi, S., Kim, A., Han, K.-M., Yoon, H.-K., Cho, S.-H., Tae, W.-S., Lee, M.-S., and Joe, S.-H. (2017). The association between substance P and white matter integrity in medication-naive patients with major depressive disorder. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-10100-y"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Humes, C., Sic, A., and Knezevic, N.N. (2024). Substance P\u2019s Impact on Chronic Pain and Psychiatric Conditions\u2014A Narrative Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115905"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/eye.2014.263","article-title":"Neuropathic ocular pain: An important yet underevaluated feature of dry eye","volume":"29","author":"Galor","year":"2014","journal-title":"Eye"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Puja, G., Sonkodi, B., and Bardoni, R. (2021). Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.764396"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Yan, H., Shan, X., Wei, S., Liu, F., Li, W., Lei, Y., Guo, W., and Luo, S. (2020). Abnormal Spontaneous Brain Activities of Limbic-Cortical Circuits in Patients with Dry Eye Disease. Front. Hum. Neurosci., 14.","DOI":"10.3389\/fnhum.2020.574758"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nbd.2015.12.017","article-title":"Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms","volume":"88","author":"Launay","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s40123-025-01115-0","article-title":"Parainflammation in the Ocular System: Considerations on the Underlying Mechanisms and Treatment of Dry Eye Disease","volume":"14","author":"Barabino","year":"2025","journal-title":"Ophthalmol. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/cxo.12849","article-title":"Molecular evidence for the role of inflammation in dry eye disease","volume":"102","author":"Ganesalingam","year":"2019","journal-title":"Clin. Exp. Optom."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"102266","DOI":"10.1016\/j.npep.2022.102266","article-title":"Role of ocular surface neurobiology in neuronal-mediated inflammation in dry eye disease","volume":"95","author":"Asiedu","year":"2022","journal-title":"Neuropeptides"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s12974-019-1656-4","article-title":"Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem","volume":"16","author":"Fakih","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e20230068","DOI":"10.5935\/0004-2749.20230068","article-title":"Effects of tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective serotonin-norepinephrine reuptake inhibitors on the ocular surface","volume":"86","author":"Ismayilov","year":"2023","journal-title":"Arq. Bras. De Oftalmol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/OPTO.S355091","article-title":"A Review of Ocular Complications Associated with Medications Used for Anxiety, Depression, and Stress","volume":"ume 14","author":"Constable","year":"2022","journal-title":"Clin. Optom."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/JCP.0000000000001382","article-title":"Dry Those Crying Eyes: The Role of Depression and Antidepressants in Dry Eye Disease","volume":"41","author":"Rakofsky","year":"2021","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jtos.2025.01.006","article-title":"Prevalence of dry eye disease in Spain: A population-based survey (PrevEOS)","volume":"36","year":"2025","journal-title":"Ocul. Surf."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/JCP.0000000000000356","article-title":"Dry Eye Related to Commonly Used New Antidepressants","volume":"35","author":"Dursun","year":"2015","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1167\/iovs.62.7.8","article-title":"Acute Inhibitory Effects of Antidepressants on Lacrimal Gland Secretion in the Anesthetized Rat","volume":"62","author":"Dankis","year":"2021","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/cxo.12415","article-title":"Influence of selective serotonin reuptake inhibitors on ocular surface","volume":"100","author":"Acan","year":"2017","journal-title":"Clin. Exp. Optom."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Chen, Q., Wei, Z., Wang, L., Xu, X., Wei, Z., Zheng, P., Cao, K., Zhang, Z., Chen, K., and Liang, Q. (2022). Dry Eye Disease in Patients with Schizophrenia: A Case-Control Study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.831337"},{"key":"ref_166","first-page":"1","article-title":"Dry Eyes Illness in Psychiatric Patients Placed on Antipsychotic Medications","volume":"12","author":"Balogun","year":"2023","journal-title":"J. Behav. Health Psychol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Mu, C., and Chen, L. (2024). Characteristics of eye disorders induced by atypical antipsychotics: A real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1322939"},{"key":"ref_168","first-page":"566","article-title":"Quantitative Analysis of Tear Film in Patients on Atypical Antipsychotics","volume":"32","author":"Dixitha","year":"2023","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Musayeva, A., Jiang, S., Ruan, Y., Zadeh, J.K., Chronopoulos, P., Pfeiffer, N., M\u00fcller, W.E., Ackermann, M., Xia, N., and Li, H. (2021). Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116133"},{"key":"ref_170","unstructured":"Haidary, H.A., and Padhy, R.K. (2025, September 19). Clozapine, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK535399\/."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3109\/15569527.2015.1018387","article-title":"The ocular surface side effects of an anti-psychotic drug, clozapine","volume":"35","author":"Ceylan","year":"2015","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_172","first-page":"191","article-title":"Tear Film Break-up Time in Bipolar Disorder","volume":"7","author":"Dibajnia","year":"2012","journal-title":"Iran. J. Psychiatry"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/15569529209042704","article-title":"The Effects of Lithium on the Human Visual System","volume":"11","author":"Fraunfelder","year":"1992","journal-title":"J. Toxicol. Cutan. Ocul. Toxicol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/YIC.0000000000000295","article-title":"Ophthalmic adverse effects of lithium","volume":"35","author":"Park","year":"2020","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.pnpbp.2009.05.007","article-title":"Sj\u00f6gren\u2019s syndrome precipiated by lamotrigine treatment","volume":"33","author":"Chuang","year":"2009","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"110104","DOI":"10.1016\/j.exer.2024.110104","article-title":"Moringa oleifera hydroalcoholic leaf extracts mitigate valproate-induced oxidative status in the extraorbital lacrimal gland in a rat model","volume":"248","author":"Oktay","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jtos.2024.01.009","article-title":"Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study","volume":"32","author":"Guo","year":"2024","journal-title":"Ocul. Surf."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1097\/ICO.0b013e3182261590","article-title":"Dry Eye Disease in Patients with Depressive and Anxiety Disorders in Shanghai","volume":"31","author":"Wen","year":"2012","journal-title":"Cornea"},{"key":"ref_179","first-page":"e76439","article-title":"Polypharmacy Associated with the Simultaneous Prevalence of Dry Eye due to Aqueous Deficiency and Hyposalivation in Adults over 50 Years Old","volume":"16","author":"Pineda","year":"2024","journal-title":"Cureus"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"285851","DOI":"10.1155\/2012\/285851","article-title":"The Role of Medications in Causing Dry Eye","volume":"2012","author":"Fraunfelder","year":"2012","journal-title":"J. Ophthalmol."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Cort\u00e9s, T., and Herrera, I. (2025). Emerging Age-Specific Therapeutic Approaches for Dry Eye Disease. J. Clin. Med., 14.","DOI":"10.3390\/jcm14124147"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"S307","DOI":"10.1097\/ICL.0000000000000463","article-title":"Neuropathic-Like Ocular Pain and Nonocular Comorbidities Correlate with Dry Eye Symptoms","volume":"44","author":"Chang","year":"2018","journal-title":"Eye Contact Lens"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1038\/s41433-024-03060-x","article-title":"Corneal neuropathic pain: A review to inform clinical practice","volume":"38","author":"Watson","year":"2024","journal-title":"Eye"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e629","DOI":"10.1097\/PR9.0000000000000629","article-title":"Evidence that dry eye is a comorbid pain condition in a U.S. veteran population","volume":"2","author":"Lee","year":"2017","journal-title":"PAIN Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1016\/j.ophtha.2017.08.004","article-title":"Neuropathic Corneal Pain","volume":"124","author":"Dieckmann","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.4103\/IJO.IJO_2981_22","article-title":"Tear biomarkers in dry eye disease: Progress in the last decade","volume":"71","author":"Kumar","year":"2023","journal-title":"Indian J. Ophthalmol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4103\/tjo.tjo_56_19","article-title":"Role of tear film biomarkers in the diagnosis and management of dry eye disease","volume":"9","author":"Shih","year":"2019","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/ICO.0000000000001206","article-title":"A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1\/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease","volume":"36","author":"Kheirkhah","year":"2017","journal-title":"Cornea"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1016\/j.ophtha.2012.03.017","article-title":"Immunomodulatory Effect of the Topical Ophthalmic Janus Kinase Inhibitor Tofacitinib (CP-690,550) in Patients with Dry Eye Disease","volume":"119","author":"Huang","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_190","first-page":"127","article-title":"Effect of recombinant human nerve growth factor eye drops in patients with dry eye: A phase IIa, open label, multiple-dose study","volume":"104","author":"Sacchetti","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"100451","DOI":"10.1016\/j.xops.2023.100451","article-title":"A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease","volume":"4","author":"Baratta","year":"2023","journal-title":"Ophthalmol. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Gou, Q., Song, Z., Gong, Y., and Li, J. (2024). TRPV1 in Dry Eye Disease. Front. Biosci., 29.","DOI":"10.31083\/j.fbl2905175"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"102347","DOI":"10.1016\/j.clae.2024.102347","article-title":"Efficacy and safety of transient receptor potential channel modulators for dry eye: A systematic review and meta-analysis","volume":"48","author":"Duan","year":"2025","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Moon, J., Jiang, E., Liu, J., Jin, H., Yoon, H.S., Choi, H.-I., Choi, J.S., Qi, H., Yoon, H.-J., and Yoon, K.C. (2025). Therapeutic Potential of Combined 5% Lifitegrast and Tocopherol Eye Drops in Managing Inflammation and Oxidative Stress in Murine Dry Eye. Pharmaceuticals, 18.","DOI":"10.3390\/ph18010038"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2147\/OPTH.S149986","article-title":"Exercise program improved subjective dry eye symptoms for office workers","volume":"12","author":"Sano","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jtos.2021.12.007","article-title":"A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study","volume":"24","author":"Chiu","year":"2022","journal-title":"Ocul. Surf."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Cammalleri, M., Amato, R., Olivieri, M., Pezzino, S., Bagnoli, P., Monte, M.D., and Rusciano, D. (2021). Effects of Topical Gabapentin on Ocular Pain and Tear Secretion. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.671238"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ophtha.2017.09.031","article-title":"Botulinum Toxin A for the Treatment of Photophobia and Dry Eye","volume":"125","author":"Diel","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_199","first-page":"2921","article-title":"The relationship between dry eye disease and anticholinergic burden","volume":"37","author":"Abay","year":"2023","journal-title":"Eye"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"87","DOI":"10.32553\/ijmbs.v8i5.2897","article-title":"Psycho Ophthalmology: The Interface Between Psychiatry and Ophthalmology","volume":"8","author":"Kumar","year":"2024","journal-title":"Int. J. Med. Biomed. Stud."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"49","DOI":"10.18433\/jpps29895","article-title":"Lifitegrast Ophthalmic Solution 5.0% for Treatment of Dry Eye Disease: Overview of Clinical Trial Program","volume":"22","author":"Chan","year":"2019","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: Validity of a brief depression severity measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J. Gen. Intern. Med."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","article-title":"A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7: The GAD-7","volume":"166","author":"Spitzer","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jare.2024.03.015","article-title":"Decoding and reconstructing disease relations between dry eye and depression: A multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization","volume":"69","author":"Chang","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Britten-Jones, A.C., Wang, M.T.M., Samuels, I., Jennings, C., Stapleton, F., and Craig, J.P. (2024). Epidemiology and Risk Factors of Dry Eye Disease: Considerations for Clinical Management. Medicina, 60.","DOI":"10.3390\/medicina60091458"},{"key":"ref_206","first-page":"528","article-title":"Dry eye in contact lens wearers as a growing public health problem","volume":"26","author":"Pili","year":"2014","journal-title":"Psychiatr Danub."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3325\/cmj.2024.65.156","article-title":"Person-centered care in ophthalmology: Current knowledge and perspectives","volume":"65","author":"Mezzich","year":"2024","journal-title":"Croat. Med. J."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Ka\u0161telan, S., Bra\u0161, M., Pjeva\u010d, N., Bakija, I., Tomi\u0107, Z., Kelemini\u0107, N.P., and Antunica, A.G. (2023). Tear Biomarkers and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713429"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1001\/jamaophthalmol.2016.4925","article-title":"Longitudinal Examination of Frequency of and Risk Factors for Severe Dry Eye Symptoms in US Veterans","volume":"135","author":"Ong","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Donthineni, P.R., Shanbhag, S.S., and Basu, S. (2021). An Evidence-Based Strategic Approach to Prevention and Treatment of Dry Eye Disease, a Modern Global Epidemic. Healthcare, 9.","DOI":"10.3390\/healthcare9010089"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.preteyeres.2024.101250","article-title":"How gut microbiota may impact ocular surface homeostasis and related disorders","volume":"100","author":"Labetoulle","year":"2024","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Kammoun, S., Rekik, M., Dlensi, A., Aloulou, S., Smaoui, W., Sellami, S., Trigui, K., Gargouri, R., Chaari, I., and Sellami, H. (2024). The gut-eye axis: The retinal\/ocular degenerative diseases and the emergent therapeutic strategies. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1468187"},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Campagnoli, L.I.M., Varesi, A., Barbieri, A., Marchesi, N., and Pascale, A. (2023). Targeting the Gut\u2013Eye Axis: An Emerging Strategy to Face Ocular Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713338"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.4103\/NRR.NRR-D-24-00531","article-title":"The gut\u2013eye axis: From brain neurodegenerative diseases to age-related macular degeneration","volume":"20","author":"Jin","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e44502","DOI":"10.2196\/44502","article-title":"Digital Phenotyping: Data-Driven Psychiatry to Redefine Mental Health","volume":"25","author":"Oudin","year":"2023","journal-title":"J. Med. Internet Res."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Parvin, N., Joo, S.W., Jung, J.H., and Mandal, T.K. (2025). Multimodal AI in Biomedicine: Pioneering the Future of Biomaterials, Diagnostics, and Personalized Healthcare. Nanomaterials, 15.","DOI":"10.3390\/nano15120895"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Wang, B. (2025). Advanced applications in chronic disease monitoring using IoT mobile sensing device data, machine learning algorithms and frame theory: A systematic review. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1510456"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T05:34:44Z","timestamp":1762320884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":217,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110699"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110699","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}