Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 7.
doi: 10.1111/aos.17556. Online ahead of print.

Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease

Mikael Thomassen Neset  1   2 , Roy Miodini Nilsen  3 , Kristian Løvås  4 , Kathrine Halsøy  1   2 , Håkon Reikvam  4   5 , Ann-Elin Meling Stokland  6 , Grethe Åstrøm Ueland  4 , Anette S B Wolff  4   5 , Hans Christian D Aass  7 , Sjur Reppe  7   8 , Eystein Sverre Husebye  4   5 , Eyvind Rødahl  1   2 , Tor Paaske Utheim  7   9 , Hans Olav Ueland  1   2
Affiliations

Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease

Mikael Thomassen Neset et al. Acta Ophthalmol. .

Abstract

Purpose: To examine ocular surface changes and inflammatory tear fluid biomarkers in patients with thyroid eye disease (TED).

Methods: We included 106 Graves' disease (GD) patients (36 without TED, 32 with active and 38 with inactive TED) and 106 age- and sex-matched healthy subjects for ophthalmological evaluation, including ocular surface status and Meibomian gland function. Tear fluid was analysed for 40 inflammatory biomarkers by a Luminex multiplex bead assay. The parameters were compared across subgroups.

Results: GD patients with TED had significantly higher median (min-max) Ocular Surface Disease Index (OSDI) score than GD patients without TED, with a median score of 31.4 (0-86.4) compared to 7.3 (0-45.8) (p < 0.01). Eleven of 50 patients with moderate-to-severe and sight-threatening TED had a meibum quality score above seven, compared to none of the 20 patients with mild TED (p = 0.027). Tear fluid levels of chemokine (C-C motif) ligand 2 (CCL2) were significantly (p = 0.003) higher in GD patients compared to healthy subjects. CD40 ligand (CD40L) and CCL2 were higher in GD patients with TED compared with GD patients without TED (p = 0.002 and 0.013, respectively). As a combined biomarker to distinguish between GD patients with and without TED, OSDI score together with tear fluid levels of CCL2 and CD40L produced an area under the receiver operating characteristic (ROC) curve of 0.80, with sensitivity of 0.69 at a fixed specificity of 0.80.

Conclusions: Our findings demonstrate increased tear fluid levels of CD40L and CCL2 in patients with TED, indicating their potential as diagnostic biomarkers. Increased ocular discomfort in patients with TED could be related to impaired meibum quality.

Keywords: CD40 ligand; Graves' disease; chemokine (C–C motif) ligand 2; dry eye disease; ocular surface disease; thyroid eye disease.

PubMed Disclaimer

References

REFERENCES

    1. Aass, C., Norheim, I., Eriksen, E.F., Børnick, E.C., Thorsby, P.M. & Pepaj, M. (2017) Establishment of a tear protein biomarker panel differentiating between Graves' disease with or without orbitopathy. PLoS One, 12, e0175274.
    1. Abraham‐Nordling, M., Byström, K., Törring, O., Lantz, M., Berg, G., Calissendorff, J. et al. (2011) Incidence of hyperthyroidism in Sweden. European Journal of Endocrinology, 165, 899–905.
    1. Aghaei, H., Zarastvand, F., Abdolalizadeh, P., Karimi, N., Es'haghi, A., Clark, J.D. et al. (2024) Meibomian gland loss and dysfunction in mild versus moderate‐severe thyroid eye disease. Journal of Current Ophthalmology, 36, 145–151.
    1. Allam, I.Y., Lazreg, S., Shaheen, M.S., Doheim, M.F. & Mohammed, M.A. (2021) Ocular surface changes in patients with thyroid eye disease: an observational clinical study. Clinical Ophthalmology, 15, 2481–2488.
    1. Avunduk, A.M., Avunduk, M.C., Pazarli, H., Oguz, V., Varnell, E.D., Kaufman, H.E. et al. (2005) Immunohistochemical analysis of orbital connective tissue specimens of patients with active Graves ophthalmopathy. Current Eye Research, 30, 631–638.

LinkOut - more resources