Orbital and retinal microvascular changes in thyroid eye disease

A new European study¹ that investigated the relationship between the orbital structural and retinal microvascular changes in patients with thyroid eye disease (TED) reported that changes in the vessel density (VD) of the deep capillary plexus (DCP) are reflective of the disease activity and structural orbital involvement, according to first author Vera Jelušić, MD. She is from the Department of Ophthalmology, University Hospital Center Osijek, and the Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, both in Osijek, Croatia.

TED, a heterogeneous condition with diverse clinical presentations, can lead to significant disfigurement.² It impacts the orbital and periocular soft tissue, and the manifestations include eyelid erythema and oedema, conjunctival hyperemia, proptosis, and diplopia, the authors explained.

“In severe cases, it can lead to loss of vision and blindness caused by compressive optic neuropathy, which occurs in approximately 3% of patients.^2,3 The exact mechanism of TED is still not fully understood, but it is assumed that autoimmune-mediated inflammation, inflammatory cell infiltration, activation of orbital fibroblasts, and hemodynamic changes in the orbit play a significant role,^4,5” they said.

TED study methodology

The investigators conducted a cross-sectional study to look at the associations between the orbital structural changes and retinal microvascular alterations in patients with TED. They also wanted to identify any clinical, biochemical, and imaging predictors of disease activity by focusing on the retinal VD and extraocular muscle thickness and orbital fat thickness as objective markers of inflammation and disease activity, they explained.

The 38 study patients (76 eyes) underwent a comprehensive ophthalmologic evaluation, Clinical Activity Score (CAS) assessment, a detailed medical history, and optical coherence tomography angiography (OCTA) to determine the VD in the superficial capillary plexus (SCP) and DCP. Magnetic resonance imaging was performed to measure the exophthalmos, extraocular muscle, and orbital fat thicknesses. The thyroid hormone levels, thyrotropin receptor antibodies (TRAb), and anti-thyroid peroxidase antibodies (anti-TPO) were measured, and a lipid profile was performed.

The patients were classified into 2 groups with active or inactive TED.

What did the analyses find in patients with TED?

Jelušić and colleagues reported that patients with active TED, defined as a CAS of 3 or higher, had significantly higher TRAb levels (P < 0.001); however, the anti-TPO levels did not differ between the active and inactive groups.

“The eyes with active eyes showed significantly higher DCP VD in the whole image (P = 0.013), parafovea (P = 0.012), and perifovea (P = 0.009) across all quadrants, with no difference in the SCP or the foveal avascular zone,” they reported.

The linear mixed model regression analyses showed that, after adjusting for previous therapy with glucocorticosteroids, the independent predictors of higher CAS values were higher triglyceride levels, greater medial rectus thickness, and whole-image DCP VD (R² = 42, P < 0.001). After adjusting for age and sex, the CAS value remained a significantly positive predictor of DCP VD in the parafovea (R² = 0.22, P < 0.001).

“Our findings provided evidence of microvascular impairment and its potential association in patients with TED. The retinal microcirculation, especially the DCP metrics, may serve as a sensitive, noninvasive biomarker reflecting both orbital inflammation and structural remodeling. Integrating OCTA with orbital imaging and metabolic profiling may improve disease activity diagnostics, TED monitoring, and potential personalized treatment strategies in TED,” Dr. Jelušić and colleagues concluded.

References

1. Jelušić V, Maduna I, Biuk D, et al. Retinal microvascular and orbital structural alterations in thyroid eye disease. J Clin Med. 2026;15:323; https://doi.org/10.3390/jcm15010323

2. Alkhadrawi AM, Lin LY, Langarica SA, et al. Deep-learning based automated segmentation and quantitative volumetric analysis of orbital muscle and fat for diagnosis of thyroid eye disease. Invest Ophthalmol Vis Sci. 2024;65:6.

3. Kahaly GJ. Management of graves thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab. 2020;105:3704–20.

4. Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J. 2016;5:9–26.

5. Ippolito S, Cusini C, Lasalvia, P, et al. Change in newly diagnosed Graves’ disease phenotype between the twentieth and the twenty-first centuries: Meta-analysis and meta-regression. J Endocrinol Invest. 2021;44:1707–18.