Lecture 4 - Metabolic Disorders of the Orbit and Adnexa

What are the two metabolic disorders of the orbit and adnexa discussed in this lecture?

Thyroid Eye Disease (TED) and Myasthenia Gravis (MG)

What are normal exophthalmometry readings in White patients?

12-22 mm

What are normal exophthalmometry readings in Black patients?

12-24 mm

What exophthalmometry difference is considered abnormal?

A difference greater than 2 mm

What is another name for Thyroid Eye Disease (TED)?

Graves' ophthalmopathy

What is another name for Thyroid Eye Disease (TED)?

Graves' orbitopathy

What is another name for Thyroid Eye Disease (TED)?

Thyroid-associated orbitopathy (TAO)

What type of disease is Thyroid Eye Disease?

A chronic, immune-mediated orbitopathy associated with thyroid disease

What thyroid disorders can be associated with TED?

Hyperthyroidism, hypothyroidism, Hashimoto disease, and Graves disease

What percentage of TED cases are associated with Graves disease?

About 90%

What are systemic symptoms of hyperthyroidism?

Rapid pulse, hot dry skin, goiter, weight loss, muscle wasting, hand tremor, and cardiac arrhythmias

What causes Graves disease?

Abnormal autoantibodies mimic natural hormones and continuously overstimulate receptors on the thyroid gland

What percentage of Graves disease patients develop TED?

25-50%

What cellular event is central to TED pathophysiology?

Abnormal activation and proliferation of orbital fibroblasts

What do orbital fibroblasts upregulate in TED?

Glycosaminoglycans (GAGs)

What is the result of GAG upregulation in orbital tissues?

Congestion and edema

What cell types do orbital fibroblasts differentiate into in TED?

Adipocytes and myofibroblasts

What is the effect of adipocyte proliferation in TED?

Fat deposition around the orbit

What is the effect of myofibroblast proliferation in TED?

Extraocular muscle enlargement

What causes increased orbital volume in TED?

Extraocular muscle swelling and orbital fat swelling

Why does the eye protrude in TED?

The increased orbital volume forces the eye forward

What occurs during the active/progressive phase of TED?

Active inflammation leads to tissue congestion

How long does the active/progressive phase of TED last?

6 months to 3 years

What is characteristic of symptoms during the active phase of TED?

Symptoms come and go

Why is intervention important during the active phase of TED?

Because active inflammation is occurring and treatment can impact disease progression

What occurs during the inactive/fibrotic phase of TED?

Spontaneous resolution and stabilization of symptoms with fibrosis

What age range is TED most commonly noted in?

Third to sixth decades of life (20s-50s)

What is the female-to-male ratio of TED?

Approximately 8:1

How does TED severity differ between men and women?

Men tend to have more severe disease and present at an older age

Is TED usually bilateral or unilateral?

Usually bilateral

What is the most important risk factor for TED?

Cigarette smoking

How much does cigarette smoking increase the risk of TED?

About 5-fold

What genetic abnormality is associated with TED?

HLA-DR3 gene abnormality

What are early nonspecific symptoms of TED?

Ocular irritation, morning eyelid puffiness, and mild discomfort

What symptoms are included under ocular irritation in TED?

Burning, foreign body sensation, photophobia, epiphora, and itching

What is a common early eyelid symptom of TED?

Morning puffiness of the eyelids

What is the most common late diplopia pattern in TED?

Variable diplopia, usually in upgaze

What eyelid finding may persist in late TED?

Persistent eyelid edema

What cosmetic issue commonly concerns patients with TED?

Changes in eye appearance from proptosis and eyelid abnormalities

What type of pain may occur in TED?

Pressure or pain behind the eye

What are causes of reduced vision in TED?

Dry eye or compressive optic neuropathy

What percentage of TED cases develop compressive optic neuropathy?

About 5%

What visual consequence can compressive optic neuropathy cause in TED?

Visual field loss

What are signs of orbital inflammation in TED?

Periorbital edema and erythema

What causes upper eyelid retraction in TED?

Increased sympathetic tone on Müller's muscle, levator contraction, and proptosis

What is Dalrymple sign?

Widening of the palpebral fissure with superior scleral show

What is lagophthalmos?

Inability to completely close the eyes

What is temporal flare in TED?

Elevation of the temporal upper eyelid above its normal anatomic location

What is Von Graefe sign?

Delayed descent of the upper eyelid during downgaze

Is Von Graefe sign a static or dynamic finding?

Dynamic

Why can IOP be higher in upgaze than primary gaze in TED?

Inferior rectus enlargement restricts upgaze and increases pressure

What is the most common cause of proptosis in adults?

Thyroid Eye Disease

What causes conjunctival injection and chemosis in TED?

Increased vascularity of enlarged extraocular muscles

Where is conjunctival injection often most pronounced in TED?

Over extraocular muscle insertions

What is exposure keratopathy?

Corneal damage caused by prolonged exposure due to lagophthalmos or exophthalmos

What causes exposure keratopathy in TED?

Prolonged corneal exposure to the environment

How does TED affect extraocular muscles?

Causes muscle thickening and restrictive myopathy

What is the order of extraocular muscle involvement in TED?

IR > MR > SR > LR > SO = IO

What mnemonic is used to remember extraocular muscle involvement in TED?

IMSLO

What is the most common strabismus pattern in TED?

Hypotropia

What is the second most common strabismus pattern in TED?

Esotropia

How does inferior rectus involvement affect ocular motility in TED?

Elevation becomes restricted

How does medial rectus involvement affect ocular motility in TED?

Abduction becomes restricted

How can TED affect the optic nerve?

Extraocular muscle enlargement can compress the nerve at the orbital apex

What pupillary sign may indicate compressive optic neuropathy in TED?

Afferent pupillary defect (APD)

What color vision change may occur with TED optic neuropathy?

Dyschromatopsia

What visual consequences can occur from TED optic neuropathy?

Vision loss and visual field loss

What optic nerve appearance may occur in TED optic neuropathy?

Optic disc edema

What percentage of TED patients develop compressive optic neuropathy?

About 5%

What are forced ductions used to evaluate in TED?

Mechanical restriction of eye movements

How are forced ductions performed?

Anesthetize the eye, grasp conjunctiva with forceps, and move the eye

What is a positive forced duction test?

Inability to move the eye in a certain direction

What alternative can be used instead of forceps during forced ductions?

A cotton swab can be used to push the eye

What are retropulsions used to assess?

How much the eye can be displaced posteriorly into the orbit

What is exophthalmometry used to measure?

Degree of proptosis

Why is visual field testing performed in TED?

To evaluate for visual field loss from compressive optic neuropathy

Why is optic nerve OCT used in TED?

To assess for optic disc edema

What imaging study is commonly used in TED?

Orbital CT scan

What thyroid tests should be ordered in TED?

T3, T4, and TSH

Who should be consulted for management of TED thyroid disease?

An endocrinologist

Why should smoking cessation be emphasized in TED?

Smoking increases the risk of progression and severity

How can eyelid and periorbital edema be managed in TED?

Cool compresses in the morning and head elevation during sleep

How can dry eye be managed in TED?

Lubrication, Restasis, Cequa, eyelid taping, or sleep masks

How can diplopia be managed conservatively in TED?

Prisms, Fresnel prisms, or occlusion

Why is treatment of the underlying thyroid disorder important in TED?

Extraocular muscle infiltration may decrease

How can Botox be used in TED?

For eyelid retraction or diplopia from extraocular muscle dysfunction

When is Botox injected into the eyelid in TED?

For eyelid retraction involving the levator muscle

When can Botox be injected into extraocular muscles in TED?

For management of diplopia

What specialist should TED patients be referred to for systemic management?

Medical internist or endocrinologist

What is Tepezza?

Teprotumumab-trbw intravenous injection therapy for TED

How many Tepezza infusions are given?

Eight infusions

How often are Tepezza infusions administered?

Every 3 weeks

How long do the first two Tepezza infusions last?

90 minutes each

How long do the remaining six Tepezza infusions last?

60 minutes each

When may extraocular muscle resection or recession surgery be used in TED?

For diplopia or extraocular muscle restriction

When are oral or IV steroids used in TED?

For optic neuropathy

What is the last-resort surgical treatment for TED?

Orbital decompression surgery

What surgical sequence follows orbital decompression surgery if additional procedures are needed?

Strabismus surgery first, then eyelid surgery

What is Myasthenia Gravis?

An antibody-mediated, T-cell dependent immunologic attack on the postsynaptic membrane endplate region

What happens to acetylcholine receptors in MG?

They are blocked and ultimately degraded