Thyroid eye disease in patients with multiple sclerosis who have been exposed to immune reconstitution therapies

Background: Immune reconstitution therapy for multiple sclerosis (MS) is associated with thyroid eye disease (TED), although this has not been described with autologous haematopoietic stem cell transplantation (AHSCT). Methods: A retrospective review of all patients with TED and MS attending a tertiary thyroid eye multidisciplinary clinic. Results: Eight women (age at MS diagnosis 23–43 years; median peak Expanded Disability Status Scale 5.75; 50% non-Caucasian) were identified between January 2015 and 2026. All received immune reconstitution therapy (alemtuzumab n=6, AHSCT n=3; one patient received both). All were previously euthyroid, and 3 had prior optic neuritis; Graves’ hyperthyroidism (GH) developed a median of 34.5 (12–49) months post-IRT and TED a median of 12 (2–35) months after GH. Presenting CAS was ≤2 in seven patients and very high TRAb levels (>30 IU/L in five patients). All developed EUGOGO moderate-to-severe TED at final review. Orbital MRI revealed marked heterogeneity of fat and extraocular muscle involvement. TED treatment included intravenous methylprednisolone (n=4), local triamcinolone (n=3), orbital decompression (n=2), strabismus surgery (n=1), and eyelid surgery (n=2). GO-QoL appearance and visual function scores were low (<75) at baseline and final visits. Conclusion: We report the first cases of TED following AHSCT for MS. Despite predominantly low CAS scores at presentation, the disease course tended towards moderate-to-severe TED at follow-up. Prolonged multidisciplinary (endocrine, ophthalmic, and neurological) vigilance with concordant radiological surveillance is recommended for this cohort. Newer biologic therapies for MS and TED raise questions about their use in patients with complex immune-modifying and reconstitution therapies.