5: Ocular Manifestations of Systemic disease - Thyroid Eye disease

Thyroid Hormone Synthesis and Regulation

• Iodine is converted into thyroid hormones T4 (thyroxine) and T3 (tri-iodothyronine).

• Iodine is combined with tyrosine to make T4 and T3.

• A normal thyroid gland produces about $80\%$ T4 and $20\%$ T3.

• Regulation by the pituitary via thyrotrophin (thyroid-stimulating hormone, TSH).

• The pituitary is regulated by the hypothalamus via thyrotropin-releasing hormone (TRH).

Graves’ Disease: Overview

• Autoimmune disorder resulting in hyperthyroidism and excessive T4 (and T3).

• Systemic manifestations: weight loss, tremor, increased sweating, heat intolerance, tachycardia, palpitations, atrial fibrillation, muscle wasting, nervousness, irritability.

• Epidemiology: more common in women aged $20-45\text{ years}$.

• Characterised by goitre (enlarged thyroid) and ophthalmopathy.

• Eye signs can occur without systemic manifestations (Ophthalmic Graves’ disease or euthyroid Graves’).

Ocular Signs of Graves’ Disease

• Upper lid retraction (Dalrymple’s sign) → overactive mullers muscle or swollen levator muscle.

• Staring frightened appearance (Kocher’s sign).

• Lid lag on downgaze (von Graefe’s sign).

• Imperfect convergence (Mobius’ sign).

• Proptosis (due to inflammation of EOMs).

• Conjunctival injection and chemosis.

• Corneal exposure with dryness, ulceration, and potential vision loss.

• Eyelid edema.

• Lacrimation, photophobia, foreign body sensation, retrobulbar discomfort.

• May also exhibit Superior Limbic Keratoconjunctivitis (SLK).

Superior Limbic Keratoconjunctivitis (SLK)

• Chronic condition affecting the superior limbus with bulbar and tarsal conjunctiva.

• About $50\%$ of sufferers have hyperthyroidism.

• Likely due to mechanical effects of the upper lid on the superior bulbar conjunctiva.

• Symptoms: chronic irritation, foreign body sensation, burning.

• Signs:

  • red papillae on the upper lid

  • hyperaemia and staining of the superior bulbar conjunctiva

  • superior punctate corneal staining

  • pannus if longstanding.

• Treatment:

  • ocular lubricants

  • short course of steroids (e.g., FML QID).

Restrictive Thyroid Myopathy

• Hyperthyroidism features enlargement of EOMs and increased orbital fat volume.

• In TED, 30–50% of patients develop ophthalmoplegia.

• Mechanism: inflammation of EOMs with fibrosis in longstanding disease; one or more EOMs are tight.

• Symptom: diplopia.

• Most common sign: elevation defect (fibrotic defect of inferior rectus, mimicking superior rectus palsy).

• Next most common defect: abduction defect (fibrotic medial rectus, mimicking sixth nerve palsy).

• Depression defect (fibrosis of superior rectus).

• Adduction defect (fibrosis of lateral rectus).

• Least commonly involved muscles: the obliques.

  

Dysthyroid Optic Neuropathy (DON)

• Seen in roughly $5\%$ of Graves’ disease cases.

• Mechanism: direct compression of the optic nerve or its blood supply at the orbital apex by congested EOMs.

• Optic neuropathy can occur with minimal or no proptosis.

• Clinical features: slow vision loss, relative afferent pupillary defect (RAPD), colour loss, any pattern of visual field loss.

• Fundus findings: vascular congestion, swelling of the optic disc, and choroidal folds.

  

Treatment of Graves’ Ophthalmopathy and Thyroid Disease

• Thyroid dysfunction management:

  • Anti-thyroid drugs: carbimazole, methimazole, propylthiouracil.

  • Radioactive iodine therapy.

  • Thyroidectomy.

• Major risk factor for developing TED (and progression to more severe disease) in Graves’ disease: smoking.

• Eye disease management:

  • Smoking cessation.

  • If mild ocular surface problems: lubricants, ointment at night, and lid taping.

  • Head elevation at night and cold compresses during the day to reduce lid oedema.

  • More severe disease: systemic steroids.

  • Optic neuropathy:

    • high-dose oral prednisolone (sometimes intravenous).

    • Orbital decompression surgery.

    • Radiotherapy.

Orbital Decompression Surgery

• A therapeutic option for severe TED

• makes more room for muscles to sit within the orbit

Hypothyroidism

• Reduced thyroid secretion; can be autoimmune or after thyroidectomy.

• Epidemiology: most common in middle-aged women.

• Clinical features: slowing of body processes (lethargy, sluggishness), reduced cold tolerance, lack of sweating, weight gain.

• Physical signs: dry scaly skin, brittle hair and nails, loss of the outer one-third of the eyebrows, swollen eyelids and tongue, swollen ankles.

• May have tear deficiency leading to keratoconjunctivitis.

• Possible retrobulbar neuritis and optic atrophy.

• Treatment: thyroid hormone supplementation typically results in dramatic improvement.