Thyroid Eye Disease: Current Perspectives in Pathogenesis, Risk Factors, and Management

Thyroid eye disease (TED), also referred to as Graves’ orbitopathy or thyroid-associated ophthalmopathy, is an autoimmune inflammatory disorder of the orbit that most often accompanies hyperthyroidism due to Graves’ disease. This review summarises current understanding of its immunopathogenesis, including the role of autoantibodies against the thyroid-stimulating hormone receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R), the subsequent activation of orbital fibroblasts, cytokine-mediated inflammation, glycosaminoglycan deposition and fibrosis. The clinical spectrum ranges from mild ocular surface irritation to sight-threatening dysthyroid optic neuropathy — and the classification systems (e.g., CAS, VISA, EUGOGO) used to assess disease activity and severity. Key modifiable risk factors such as smoking, uncontrolled thyroid status, micronutrient deficiencies (selenium, iron, iodine), dyslipidaemia, and vitamin D deficiency are reviewed. We present management strategies from achieving euthyroidism and risk-factor control, to supportive care (lubrication, eyelid taping) and medical therapies — from high-dose intravenous methylprednisolone to immunosuppressants (mycophenolate, azathioprine) and novel biologics such as teprotumumab (anti-IGF-1R), rituximab (anti-CD20) and tocilizumab (anti-IL-6R). Surgical options (orbital decompression, strabismus correction, eyelid surgery) for disfiguring or sight-threatening disease are discussed. Finally, we highlight future directions including biomarker development and personalised, mechanism-based therapy. Early recognition and intervention, along with risk factor modification and targeted treatments, may improve functional and psychosocial outcomes in TED.