Thyroid Eye Disease: Early Clinical Recognition and Differential Diagnosis

 

Thyroid Eye Disease: Early Clinical Recognition and Differential Diagnosis 

Introduction

Thyroid Eye Disease (TED), also known as thyroid-associated orbitopathy, is the most common cause of orbital inflammation in adults. It is an autoimmune condition strongly linked to Graves’ disease but may also occur in euthyroid or hypothyroid patients. Autoantibodies stimulate orbital fibroblasts—particularly those expressing TSH receptor and IGF-1 receptor—leading to expansion of extraocular muscles and orbital fat. Early recognition is critical, as timely referral and co-management can prevent sight-threatening complications such as compressive optic neuropathy and severe exposure keratopathy.

Early Signs and Symptoms

TED often begins subtly, and clinicians should maintain a high index of suspicion in patients with known thyroid dysfunction or recent systemic symptoms. Early ocular symptoms include foreign body sensation, dryness or watering, photophobia, peri-orbital aching, and intermittent diplopia. Patients may also report a feeling of ocular fullness or pressure, especially on waking.

 

Key early clinical signs include:

1.Eyelid Retraction– the most characteristic early sign. Look for upper lid scleral show or lateral flare.

2.Lid Lag (von Graefe’s sign)– delay of the upper lid on downgaze.

3.Periorbital Edema– inflammatory swelling of the eyelids and surrounding tissues.

4.Conjunctival Injection, especially over muscle insertions (sectoral redness).

5.Mild Proptosis– detectable with Hertel exophthalmometry; asymmetry of >2 mm is significant.

Resistance to Retropulsion– suggests early orbital congestion.

Extraocular Motility Restriction– usually inferior rectus first (limiting elevation), followed by medial rectus (limiting abduction).

Tear film instability– due to lacrimal gland involvement and increased exposure.

 

Early Red Flags (Urgent Referral)

Reduced colour vision

Relative afferent pupillary defect

Optic disc swelling

Rapid-onset constant diplopia

Visual acuity deterioration

These signs may indicate optic nerve compression.

 

Differential Diagnosis

Many conditions can mimic early TED, especially those presenting with lid swelling, redness, or motility disturbance. Important differentials include:

1.Allergic Conjunctivitis– bilateral itching, papillae, seasonal pattern; lacks motility restriction or lid retraction.

2.Orbital Cellulitis– acute painful proptosis, fever, and marked EOM limitation; systemic illness is typical.

3.Idiopathic Orbital Inflammation (Orbital Pseudotumor)– rapid onset pain and motility limitation but usually unilateral; responds quickly to corticosteroids.

4.Myasthenia Gravis– causes variable ptosis and diplopia but *never* causes proptosis, lid retraction, or resistance to retropulsion.

5.Orbital Tumours– slow progressive unilateral proptosis; may show displaced globe or palpable mass.

6.Chronic Blepharitis – may mimic periocular swelling but does not cause extraocular muscle involvement.

Conclusion

TED is a common but potentially sight-threatening orbital disorder. Clinicians must be vigilant in detecting early symptoms—especially eyelid retraction, periorbital swelling, and subtle diplopia—in patients with current or past thyroid dysfunction. Accurate differentiation from other orbital pathologies allows timely referral and multidisciplinary management, ultimately improving patient outcomes.

References

1. Bahn, R.S. (2010). Graves' Ophthalmopathy.New England Journal of Medicine, 362(8), 726–738.

2. Bartalena, L., Kahaly, G.J., Baldeschi, L., et al. (2021). The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines.European Journal of Endocrinology, 185(4), G43–G67.

3. Rootman, J. (2022).Diseases of the Orbit: A Multidisciplinary Approach (4th ed.). Wolters Kluwer.

4. American Academy of Ophthalmology. (2024).Orbital Disease and Thyroid Eye Disease: Basic and Clinical Science Course.

5. Douglas, R.S., et al. (2020). Teprotumumab for the Treatment of Active Thyroid Eye Disease.New England Journal of Medicine, 382, 341–352.

6. Bartley, G.B. (1994). The Epidemiologic Characteristics and Clinical Course of Ophthalmopathy Associated with Autoimmune Thyroid Disease.Ophthalmology, 101(2),