{
  "abstract": "Background Thyroid eye disease (TED) is a complex autoimmune disorder that is frequently disfiguring and sight-threatening. Recent advances have shifted treatment from surgery toward targeted biologic therapies like teprotumumab (TMB), an IGF-1R inhibitor that improves proptosis, diplopia, and inflammation. However, ocular surface symptoms often persist. Methods We conducted a longitudinal pre-post comparative study of patients with active, moderate-to-severe TED treated with TMB at a tertiary academic medical center, with tear sampling at two prespecified time points: baseline (collected within the 3 weeks strictly antecedent to the first infusion) and post-treatment (within 6 months of the final infusion). Adults with active, moderate-to-severe TED who received ≥4 TMB infusions were eligible. All patients contributed paired pre- and post-treatment tear samples (22 eyes). Controls were adults without TED or ocular surface disease (32 eyes). Tear fluid was collected by Schirmer strips and analyzed by liquid chromatography-tandem mass spectrometry. Differential expression was assessed using a linear mixed-effects model to explicitly account for the intrinsic correlation between paired eyes; correlations between LFQ intensities and clinical metrics used Spearman rank correlation. Results A total of 2974 proteins were identified across 76 tear samples. Unsupervised analyses demonstrated separation between control, pre-treatment, and post-treatment TED tear proteomes. Although TMB induced substantial proteomic changes, post-treatment profiles did not revert to a control-like state. Proteins involved in inflammation, oxidative stress, and cytoskeletal organization remained persistently dysregulated, while a subset of tear film stability–associated proteins normalized. Several persistently dysregulated protein targets overlapped with FDA-approved drugs. Conclusions These observational findings support tear proteomics as a platform for biomarker discovery and therapeutic prioritization and warrant validation in larger, independent cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Molecular Surgery Laboratory, Stanford University",
    "Departments of Physiology and Pharmacology & Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary",
    "Department of Ophthalmology, Byers Eye Institute, Stanford University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gabriel Velez"
    },
    {
      "affs": [
        0
      ],
      "name": "Gia-Han Ngo"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Young"
    },
    {
      "affs": [
        2
      ],
      "name": "Linus Amarikwa"
    },
    {
      "affs": [
        1
      ],
      "name": "Antoine Dufour"
    },
    {
      "affs": [
        2
      ],
      "name": "Andrea L. Kossler"
    },
    {
      "affs": [
        0
      ],
      "name": "Vinit B. Mahajan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ak1cdqees1d6s.bib",
  "cited_by": 1,
  "doi": "10.1038/s43856-026-01757-6",
  "fulltext_url": "https://doi.org/10.1038/s43856-026-01757-6",
  "id": "ak1cdqees1d6s",
  "issns": [
    "2730-664X"
  ],
  "landing_url": "https://doi.org/10.1038/s43856-026-01757-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2739|Ocular Surface and Contact Lens"
    ]
  ],
  "openalex": "W7166676922",
  "pdf_url": "https://www.nature.com/articles/s43856-026-01757-6_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/ak1cdqees1d6s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:29Z",
      "native_id": "efe033b5d60844b7810630d05138a83a",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s43856-026-01757-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Ocular Surface and Contact Lens",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease",
  "title_text": "Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:29Z",
  "url": "https://research.draconitic.com/paper/ak1cdqees1d6s",
  "venue": "Communications Medicine",
  "versions": []
}