Thyroid Eye Disease: Symptoms, Types, Causes and Treatment

Thyroid Eye Disease (TED), also known as Graves’ ophthalmopathy or thyroid-related ophthalmopathy, is a complex condition that affects the eyes and the tissues around them. While not everyone with thyroid issues develops TED, the disease can be distressing and, in severe cases, sight-threatening. Understanding the symptoms, the different types, underlying causes, and evolving treatment options is crucial for patients, caregivers, and clinicians alike. Let’s take a comprehensive look at this multifaceted disease.

Symptoms of Thyroid Eye Disease

When it comes to TED, symptoms can range from mild and barely noticeable to severe and life-altering. People often notice changes in their eyes or vision before they even realize they have a thyroid problem. The symptoms can affect daily life and are not just cosmetic—they can have a significant impact on physical comfort and mental well-being.

Symptom	Description	Severity Range	Source(s)
Proptosis	Bulging of the eyes	Mild to severe	1, 3, 4
Eyelid Retraction	Upper eyelid pulled back	Mild to severe	1, 3, 5
Double Vision	Seeing two images	Moderate to severe	1, 3, 4
Eye Pain/Irritation	Redness, pain, grittiness	Mild to severe	1, 4, 5
Visual Loss	Decreased or lost vision	Severe/sight-threatening	1, 3, 5
Dryness/Tearing	Feeling of dryness or excessive tearing	Mild to moderate	4, 5
Soft Tissue Swelling	Swelling around eyes and eyelids	Mild to moderate	3, 4, 5

Table 1: Key Symptoms

Overview of TED Symptoms

TED doesn’t present the same way in every patient. The most recognizable symptom is "proptosis," where the eyes seem to bulge forward. This occurs because the tissues and muscles behind the eye become inflamed and swollen. Other hallmark signs include eyelid retraction, where the upper eyelid is pulled back making the person appear to be staring, and double vision, which can significantly disrupt daily activities 1, 3, 4.

Mild, Moderate, and Severe Symptoms

• Mild symptoms: Dryness, redness, irritation, and a gritty feeling in the eyes are common early complaints. Some people notice excessive tearing or mild puffiness 4, 5.
• Moderate symptoms: Proptosis and eyelid retraction become more noticeable, and double vision can occur as the muscles controlling eye movement are affected 1, 3.
• Severe symptoms: Sight-threatening issues like decreased or lost vision may develop, usually from pressure on the optic nerve or corneal ulcers. These require urgent medical attention 1, 3, 5.

Quality of Life Impact

Symptoms can persist even after inflammation subsides, affecting a person’s appearance, confidence, and mental health. Many patients report ongoing discomfort or changes in self-image, leading to anxiety or depression 4.

Types of Thyroid Eye Disease

TED is not a one-size-fits-all diagnosis. It manifests in different forms and passes through distinct phases. Classifying the disease helps guide treatment and predict outcomes.

Type/Phase	Key Features	Severity/Progression	Source(s)
Inflammatory	Active swelling, redness	Early, more severe	4, 2, 3
Non-inflammatory	Persistent symptoms but no active inflammation	Later, often chronic	4, 2
Type 1 (Lipogenic)	Predominant fat expansion, minimal muscle involvement	Milder, atypical	9, 2
Type 2 (Myogenic)	Muscle enlargement, diplopia, restricted movement	Often more severe	3, 9, 2
Severity Grades	Mild, Moderate-to-Severe, Sight-Threatening	Guides management	2, 5, 3

Table 2: Types and Phases of TED

Disease Phases: Inflammatory vs. Non-inflammatory

• Inflammatory (Active) Phase: Characterized by redness, swelling, and pain around the eyes. This phase is when the immune system is most aggressively attacking the orbital tissues. Symptoms tend to be more severe and rapidly changing 4, 2.
• Non-inflammatory (Inactive/Chronic) Phase: Inflammation subsides, but the changes caused by earlier swelling can persist, such as proptosis, double vision, and eyelid changes. These symptoms often remain for years, affecting appearance and function 4.

Subtypes Based on Tissue Involvement

• Type 1 (Lipogenic): Fat tissue expansion dominates, causing bulging (proptosis) but less muscle involvement. Atypical cases can present with unusual features, such as eyelid droop or “pseudoptosis,” without obvious muscle swelling 9.
• Type 2 (Myogenic): Extraocular muscles are primarily affected, leading to restricted eye movements and double vision. This type is usually more severe and can lead to significant functional problems 3, 9.

Severity Grading

• Mild: Symptoms are noticeable but not disabling. Most hypothyroid TED patients fall into this category, often presenting with dry eye 5.
• Moderate-to-Severe: More pronounced symptoms, such as marked proptosis, diplopia, or significant soft tissue involvement. Hyperthyroid patients are more likely to have this grade 5.
• Sight-Threatening: Rare but critical. Includes optic nerve compression and corneal ulcers, requiring urgent intervention 2, 3, 5.

Causes of Thyroid Eye Disease

Understanding what triggers TED is essential for prevention and management. It’s a multifactorial autoimmune disease, meaning the body’s own immune system mistakenly attacks tissues around the eyes. While it is most commonly linked with Graves’ disease (an autoimmune hyperthyroidism), TED can also occur in people with hypothyroidism or even normal thyroid function.

Cause/Factor	Description	Relative Risk	Source(s)
Autoimmunity	Immune attack on orbital tissues	Primary cause	1, 3, 8
TSH Receptor Antibodies	Antibodies stimulate orbital fibroblasts	Major trigger	8, 10, 13
IGF-1 Receptor	Promotes tissue growth/inflammation	Key role	8, 10, 13
Thyroid Status	Hyperthyroid > Hypothyroid > Euthyroid	Hyperthyroid highest risk	6, 5
Smoking	Increases risk 7–8 fold	Major modifiable risk	3
Genetics/Other	Family history, oxidative stress	Additional factors	10, 3

Table 3: Key Causes and Risk Factors

Autoimmune Mechanisms

TED develops when the immune system targets proteins shared by the thyroid gland and the tissues around the eyes. The most important of these is the thyroid-stimulating hormone receptor (TSHR), found on orbital fibroblasts. Antibodies that stimulate TSHR activate these cells, causing them to secrete substances (like glycosaminoglycans and hyaluronan) that attract water and cause swelling 8, 10, 13.

The Role of IGF-1 Receptor

Recent research has shown that the insulin-like growth factor 1 receptor (IGF-1R) is also highly expressed in orbital tissues. Activation of IGF-1R, often in combination with TSHR, amplifies inflammatory and tissue-expanding signals. This crosstalk is central to disease development and is now a major therapeutic target 8, 10, 13.

Thyroid Function and TED

• Hyperthyroidism (Graves’ Disease): Most common in TED; about 86% of TED patients have hyperthyroidism 6.
• Hypothyroidism: Seen in about 10% of TED cases; usually milder symptoms 5, 6.
• Euthyroid TED: A minority of patients have normal thyroid function tests but still develop TED 6.

Environmental and Lifestyle Risks

• Smoking: The single most important modifiable risk factor. Smokers have a 7–8 fold increased risk of developing TED. Smoking also worsens disease severity and reduces response to treatment 3.
• Genetics and Other Factors: Family history, oxidative stress, and certain molecular pathways (such as CD40:CD154) can influence susceptibility and severity 10, 3.

Treatment of Thyroid Eye Disease

TED management has evolved rapidly, moving from broad-acting steroids to precision-targeted therapies. Treatment aims to reduce inflammation, preserve vision, improve appearance, and restore quality of life. The choice depends on disease phase, severity, and patient preference.

Treatment	Mechanism/Target	When Used	Source(s)
Corticosteroids	Suppress immune response	Active, moderate-to-severe	12, 15, 2
Traditional Immunosuppressants	Broad immune modulation	Refractory or adjunct	12, 15
Biologics (Teprotumumab)	IGF-1R inhibition	Active, moderate-to-severe	11, 12, 13, 15
Radiation Therapy	Reduces inflammation	Severe, vision-threatening	13, 15
Surgery	Decompression, strabismus, eyelid	Chronic, sight-threatening	15, 13, 2
Lifestyle/Supportive	Stop smoking, lubricants	All stages	3, 10

Table 4: Treatment Approaches in TED

Medical Therapy

• Corticosteroids: Intravenous steroids are the mainstay for active, moderate-to-severe TED. They reduce inflammation but can have significant side effects and don’t always alter the course of the disease 12, 15.
• Traditional Immunosuppressants: Drugs like mycophenolate, tocilizumab, and rituximab may be used as adjuncts or when steroids fail 12, 15.

Targeted Biologic Therapies

• Teprotumumab: The first FDA-approved targeted therapy for TED, teprotumumab is a monoclonal antibody that blocks IGF-1R. It has shown efficacy in reducing proptosis, improving double vision, and enhancing quality of life in clinical trials 11, 12, 13, 15.
• Emerging Therapies: Other biologics targeting B cells, cytokines, and TSHR are in development. Drugs like linsitinib (an IGF-1R inhibitor) and FcRn blockers are under investigation and may broaden non-surgical options 14, 13, 15.

Radiation and Surgery

• Radiation Therapy: Sometimes used for severe, vision-threatening TED or when other treatments fail 15, 13.
• Surgery: Reserved for chronic, stable disease or urgent cases (e.g., optic nerve compression). Surgical options include orbital decompression, strabismus correction, and eyelid surgery 15, 13, 2.

Supportive and Lifestyle Measures

• Smoking cessation: Strongly recommended for all patients, as it improves outcomes and reduces risk 3, 10.
• Lubricating eye drops: Help manage dryness and irritation in all stages.
• Thyroid function control: Achieving and maintaining normal thyroid hormone levels is essential 10, 6.

Conclusion

Thyroid Eye Disease is a complex, life-altering condition requiring a multidisciplinary and individualized approach. Recent advances in understanding its autoimmune and molecular underpinnings have led to the emergence of targeted therapies, offering new hope for patients.

Key takeaways:

• TED causes a wide range of eye symptoms, from mild discomfort to vision loss.
• It exists in inflammatory (active) and non-inflammatory (chronic) phases, and can be classified by tissue involvement and severity.
• The disease is primarily autoimmune, involving TSHR and IGF-1R pathways, and is strongly linked to hyperthyroidism (but can occur with other thyroid states).
• Smoking greatly increases the risk and severity of TED.
• Treatments now range from steroids and immunosuppressants to highly targeted biologics like teprotumumab, with surgery reserved for specific cases.
• Lifestyle measures, especially quitting smoking and controlling thyroid hormones, remain important for all patients.

Early recognition and a tailored, multidisciplinary treatment plan can help patients navigate TED, preserve their vision, and reclaim their quality of life.