Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease
- 1Molecular Surgery Laboratory, Stanford University
- 2Departments of Physiology and Pharmacology & Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary
- 3Department of Ophthalmology, Byers Eye Institute, Stanford University
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.
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BibTeX
@article{velez2026paired,
title = {{Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease}},
author = {Gabriel Velez and Gia-Han Ngo and Daniel Young and Linus Amarikwa and Antoine Dufour and Andrea L. Kossler and Vinit B. Mahajan},
journal = {Communications Medicine},
year = {2026},
month = jun,
doi = {10.1038/s43856-026-01757-6},
url = {https://doi.org/10.1038/s43856-026-01757-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease
AU - Gabriel Velez
AU - Gia-Han Ngo
AU - Daniel Young
AU - Linus Amarikwa
AU - Antoine Dufour
AU - Andrea L. Kossler
AU - Vinit B. Mahajan
PY - 2026
DA - 2026/06/01
JO - Communications Medicine
DO - 10.1038/s43856-026-01757-6
UR - https://doi.org/10.1038/s43856-026-01757-6
AB - 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.
SN - 2730-664X
ER -