Overview 

Thyroid eye disease is an autoimmune disorder that commonly occurs in Graves’ disease patients but can also occur in patients with Hashimoto’s thyroiditis or euthyroid individuals.¹ The condition is characterised by swelling of the extraocular muscles leading to proptosis.² In severe cases, it may lead to eye movement issues and diplopia.

TED affects both paediatric and adult populations.  Based on research, an estimated 33% to 67% ³ of patients with juvenile Graves' disease develop TED, with higher prevalence in teenagers (68.2%) than in younger children (31.8%).In adults, around  60% of Graves' disease patients are affected with TED, with peak incidence in the 40-49 and 60-69 age groups.⁴ Females are more susceptible in paediatric cases, while adults show a bimodal sex distribution.¹

The onset of TED in both populations shares multiple risk factors like ethnicity, gender, genetics, systemic conditions, environmental factors, and trauma.⁵ The severity of TED varies, with children exhibiting milder symptoms than adults. These differences influence the management of the disease. 

Clinical presentation of TED in children and adolescents

Although there are fewer studies of the physiology of TED in paediatrics, the cascade of mechanisms leading to its development is similar to that of an adult population.⁶ Common symptoms include pain, foreign body sensation, hypersensitivity to light (photophobia), excessive tearing, and, less frequently, diplopia. Clinical signs such as Graefe’s sign (lid lag), eyelid retraction (typically upper eyelid), and soft tissue involvement are often prominent.⁷ Proptosis is less severe than in adults due to differences in orbital anatomy. Serious complications like damage to the cornea, strabismus, and dysthyroid optic neuropathy (DON) are more pronounced as the disease progresses in adolescence.⁸

Children with TED are at increased risk of developing myopia. This is due to structural changes in the eye that occur with TED, such as the enlargement of extraocular muscles and remodelling of the orbital tissue. These changes can affect the shape of the eye, leading to elongation of the optical axis and contributing to myopia progression.

Childhood to Adolescence is a critical period when vision development is still ongoing. Any changes in the orbital structure and eye muscles can disrupt normalcy and worsen TED.

Clinical presentation of TED in adults

Most adult TED patients exhibit severe manifestations compared to paediatric cases.  In the early stages, redness, irritation, and discomfort of the eyes and eyelids are common. This progresses to the retraction of eyelids, which exposes the eyes. At this stage, thyroid eye disease is often misdiagnosed as allergic conjunctivitis, which has the same symptoms. However, the most noticeable sign which can help to differentiate is the exophthalmos or bulging of the eyes. This can give the appearance of a characteristic staring” appearance.

Further, the patient may develop diplopia and strabismus. Progressive oedema can enlarge the eye muscles and cause damage to the optic nerve, which carries nerve impulses to the brain. 

The natural course of thyroid eye disease in adults follows Rundle’s curve,¹⁰ progressing through distinct phases:

• Active (inflammatory) phase: The disease worsens progressively due to acute inflammation.Peak phase: Spontaneous improvement begins, typically lasting 1–2 years
• Chronic ("burnt-out") phase: The disease becomes inactive, with further changes unlikely

While some patients experience spontaneous improvement, many adult patients will have persistent long-term symptoms. They will need a timely diagnosis, medical or surgical intervention to prevent serious implications.

Management of TED in children and adolescents

Thyroid eye disease management in children mainly focuses on early diagnosis and preventing the long-term complications. While the disease is milder in paediatric cases, timely intervention is very important to reduce the risk and support normal eye development. Treatment is tailored based on the patient’s age, disease severity, and any associated comorbidities.

Attaining Euthyroidism: Addressing the underlying immunological cause, by restoring normal thyroid levels, is the priority in the course of treatment for children. Currently, the available treatment options include antithyroid drugs (ATDs), radioactive iodine therapy (RAI), and thyroidectomy surgery.¹¹  According to the American Thyroid Association, ATDs serve as the first line of treatment.¹² Radioactive iodine therapy (RAI) or thyroidectomy is to be considered if ATDs are not tolerated or relapse occurs.

 ATD therapy can be initiated in younger children to postpone RAI until adolescence, so that the risks of radiation can be reduced. Methimazole is the most commonly prescribed drug for ATD therapy.¹³ Though ATD causes minor side effects like pruritus, rash, urticaria, oedema, arthralgias and arthritis, and granulocytopenia,¹² they resolve within weeks.

If the ATD therapy fails, RAI is commonly recommended as the next therapeutic option.. This treatment involves beta radiation being delivered to the thyroid glands via an oral capsule, which destroys the thyroid follicular cells, causing hypothyroidism. Hypothyroidism is then managed by administering hormonal replacement therapy. Moreover, treating hypothyroidism also minimises the risk of malignancy of the radiated thyroid cells in situ.^{13, 14} However, due to radiation safety concerns, RAI is generally contraindicated in children under 5 years of age, with treatment typically deferred until adolescence when possible.

Thyroidectomy is usually performed in cases when the patient is less than 5 years of age and is exhibiting hyperthyroidism despite ATD or RAI.¹³ Even though thyroidectomy reduces the clinical symptoms of TED, it creates a hypothyroid state. As a result, thyroid hormone replacement therapy for the lifetime needs to be initiated. Postoperative monitoring is crucial, particularly for potential complications such as hypocalcemia. Importantly, surgical risks demonstrate an inverse relationship with age, with the highest complication rates observed in younger children.

 Post-Euthyroidism: After achieving a euthyroid state, pediatric TED can be managed by focusing on controlling the ocular symptoms and preventing long-term complications. Ocular symptoms are usually managed in the conventional ways by prescribing corticosteroids.¹⁶ While use of oral corticosteroids, such as prednisolone or dihydrocortisone, has been reported, intravenous corticosteroids with weight-based dosing according to the Kahaly protocol are generally preferred for better outcomes.¹⁷ However, clinicians must remain vigilant about potential adverse effects of prolonged steroid use, including weight gain, growth impairment, immunosuppression, hepatotoxicity, and cardiovascular risks.¹⁸

In very rare conditions, orbital decompression or eyelid surgeries may be required.¹⁹ Additionally, the immunotherapy avenues with drugs like Teprotumumab can be explored for adolescents after their growth ceases.²⁰   

Management of TED in adults    

While the fundamental management of TED is consistent across all age groups, adult patients exhibit a range of severity and associated morbidities. Hence, an aggressive treatment plan is required, especially in moderate to severe disease conditions. 

Mild active TED: The first line of treatment in adult cases of TED is also to achieve Euthyroidism. Once attained, supportive treatments to keep a watch on the ocular inflammation are sufficient for the mild cases. This can be done by strictly avoiding tobacco if the patient is a smoker and lubricating the eyes with drops or ointments to reduce drying. Consumption of around 100 μg of selenium twice a day has also been recommended at this stage of TED.²³ Selenium incorporates into selenocysteine-containing proteins, which are believed to have an immunomodulatory effect on eye muscle inflammation.²⁴ To temporarily correct eyelid retraction, Botox injections can also be considered.²⁵

Moderate to Severe active TED:  Once the disease enters this stage, an aggressive treatment plan for immunosuppression is required. A pulse therapy of intravenous corticosteroid, like methylprednisolone, is usually administered.²⁶ However, steroid withdrawal may occasionally precipitate disease flare-ups, necessitating alternative second-line interventions:  

1. Orbital radiotherapy (ORT):²⁷ The activated orbital fibroblasts and inflammatory cells are targeted with a low dosage of radiation, which reduces disease progression. Although ORT lowers the long-term use of steroids, there are some potential risk factors like malignancy, cataract formation and retina damage
2. Immunomodulators and Immunobiologicals:  Immunomodulators like Methotrexate,²⁸ inhibit T cell and B cell proliferation, thereby controlling the overactive immune system and preventing ocular tissue damage. Immunobiologicals like Tocilizumab,²⁹ are monoclonal antibodies which block the inflammatory cytokines, stalling the excessive inflammation of the ocular tissues

Moderate to severe inactive TED: Elective surgical options are the only answer to treat this stage of TED. After ensuring that the disease is in the stable inactive form for more than 6 months, the surgical management plan is tailored as per the patient’s needs. The surgical plan is customised to each patient's needs and typically follows a staged protocol:

1. Initially, orbital decompression surgery.^30,31 is conducted to correct proptosis
2. A follow-up strabismus surgery is performed after six months to achieve adequate ocular alignment⁵
3. Later, a definitive lid retraction surgery is recommended to restore the cosmetic and functional status

Note: Not all patients require every surgical stage - the sequence is tailored to the individual’s presentation.

Along with the medical and surgical procedures, addressing the mental health of the individuals should be a part of the management plan for TED.  As thyroid eye disease causes a lot of noticeable changes in a person’s appearance, it affects the emotional well-being, and the patients often experience depression ³¹. Therefore, psychological consultation should also be recommended as a part of a treatment plan.

Summary

Thyroid Eye Disease (TED) presents differently in children and adults and hence needs an age-specific management strategy. The Pediatric TED is often milder, with eyelid retraction as one of the major symptoms, whereas Adult TED involves orbital inflammation and progressive proptosis.

In terms of management, achieving euthyroidism with ATDs, RAI, or thyroidectomy is the primary goal for both age groups. ATDs are preferred in children, and RAI for adults. When these fail, thyroidectomy is preferred in both cases.

After euthyroidism, ocular management in both groups is by Corticosteroids. With intravenous route is preferred in children, and a combination of both oral and intravenous dosage is preferred for adults. Surgeries like Orbital decompression and strabismus are rarely needed by children, but are common in adults. Long-term monitoring remains essential in both groups to prevent relapse and address ocular complications effectively.