19 Intro to diplopia diagnosis and management

What are the common clinical signs that suggest orbitopathy?

Orbitopathy commonly presents with red eye, proptosis, conjunctival chemosis, and ocular motility restriction. Motility restriction can cause strabismus and diplopia.

Why can orbitopathy cause diplopia or strabismus?

Orbital inflammation, congestion, or mass effect can restrict extraocular muscle movement, leading to ocular motility limitation, misalignment, and diplopia/strabismus.

What is a carotid-cavernous fistula?

A carotid-cavernous fistula is an abnormal communication between the carotid arterial system and the cavernous sinus, causing venous congestion in the orbit.

What are the key ocular findings of a carotid-cavernous fistula?

Key findings include red eye, proptosis, ophthalmoplegia, diplopia, engorged conjunctival vessels, elevated IOP, and possible RAPD, iris neovascularization, or retinal involvement.

What symptoms and vision findings can occur in carotid-cavernous fistula?

Patients may have normal to poor visual acuity, headache, red eye, and diplopia. Vision may worsen if there is optic nerve, retinal, or ischemic involvement.

How are carotid-cavernous fistulas treated, and what is the prognosis?

High-flow fistulas may require surgical or endovascular treatment. Some low-flow fistulas can be observed if there is no high IOP or worsening symptoms. Prognosis is generally good.

What is thyroid eye disease, and what systemic condition is it commonly associated with?

Thyroid eye disease, or Graves ophthalmopathy, is an autoimmune orbital disease associated with generalized thyroid overactivity, usually Graves disease/hyperthyroidism, and may cause orbitopathy.

What are common symptoms of thyroid eye disease?

Common symptoms include ocular irritation, red eye, blurred vision, diplopia, and other orbitopathy signs such as proptosis or motility restriction.

What is the mechanism behind diplopia and proptosis in thyroid eye disease?

Autoimmune inflammation causes enlargement and fibrosis of orbital tissues and extraocular muscles, leading to proptosis and restricted eye movement, which can cause diplopia.

What are risk factors for thyroid eye disease?

Risk factors include Graves disease/hyperthyroidism, smoking, increasing age, and potentially worsening after treatment of hyperthyroidism, especially radioactive iodine in some patients.

What does the NOSPECS classification describe in thyroid-associated ophthalmopathy?

NOSPECS grades thyroid eye disease from no disease to sight-threatening disease:
No signs/symptoms, Only signs, Soft tissue involvement, Proptosis, Extraocular muscle involvement, Corneal involvement, Sight loss.

What are the early NOSPECS findings in thyroid eye disease?

Early findings include no symptoms, then only signs such as lid retraction, followed by soft tissue periorbital swelling. Lid retraction is very common and occurs in about 90%.

What are the intermediate NOSPECS findings in thyroid eye disease?

Intermediate disease includes proptosis and extraocular muscle involvement. Proptosis occurs in about 60%, while EOM involvement occurs in about 40% and may progress from limitation to restriction to globe fixation.

What are the severe, sight-threatening NOSPECS findings in thyroid eye disease?

Severe findings include corneal exposure disease and optic neuropathy with sight loss. Optic neuropathy is uncommon, about 5%, but high-yield because it can cause decreased VA, field defects, disc swelling/pallor, and severe vision loss.

What is the typical clinical course of thyroid eye disease?

Thyroid eye disease is usually self-limiting, with an active inflammatory phase where signs and symptoms worsen, followed by a plateau, then an inactive/fibrotic phase.

Why does thyroid eye disease require close monitoring even though it is often self-limiting?

Patients must be monitored for progression to compressive optic neuropathy, which can threaten vision. Follow-up should include visual acuity, color vision testing, and self-monitoring for red desaturation.

What vision findings suggest progression to optic neuropathy in thyroid eye disease?

Concerning findings include decreased visual acuity, reduced color vision/red desaturation, visual field defects, and possible disc swelling or pallor.

What are the main treatment categories for thyroid eye disease?

Treatment includes control of the abnormal thyroid state, systemic steroids, surface disease treatment, diplopia management, orbital radiotherapy, orbital decompression, and extraocular muscle surgery.

How is inflammatory or active thyroid eye disease treated?

Active inflammatory disease may require systemic steroids and sometimes orbital radiotherapy, while also treating dry eye or exposure-related surface disease.

When is orbital decompression used in thyroid eye disease?

Orbital decompression is used for significant proptosis or compressive optic neuropathy. In optic neuropathy, decompression can often result in immediate vision improvement.

How are diplopia and motility restriction managed in thyroid eye disease?

Diplopia can be managed symptomatically during active disease, but persistent restrictive strabismus may require extraocular muscle surgery, usually after the disease becomes inactive/stable.

What is Tepezza, and what is its role in thyroid eye disease?

Tepezza, generic name teprotumumab, is a newer nonsurgical treatment approved in 2020 for active thyroid eye disease. It is used to reduce disease activity and especially proptosis.

What clinical trial outcome supported Tepezza approval for thyroid eye disease?

In two studies of patients with active TED, Tepezza produced a greater than 2 mm reduction in proptosis in 71% of patients in Study 1 and 83% in Study 2, compared with 20% and 10% in placebo groups.

What is the major clinical benefit of Tepezza in TED?

Tepezza significantly reduces proptosis, or eye protrusion, in active thyroid eye disease, making it a nonsurgical option before considering orbital decompression in selected patients.

What type of drug is Tepezza, and what receptor does it target?

Tepezza is a monoclonal antibody that antagonizes activity at the IGF-1 receptor, which is highly expressed by orbital fibroblasts in active thyroid eye disease.

What is the proposed mechanism of Tepezza in thyroid eye disease?

Tepezza blocks IGF-1R signaling on orbital fibroblasts, reducing the orbital inflammatory and tissue remodeling processes that contribute to proptosis and active TED signs.

How is Tepezza administered, and what is a practical limitation of treatment?

Tepezza is given by IV infusion. A major practical limitation is high cost, with full treatment over about 6 months costing around $200,000 and potentially more in larger patients.

Besides thyroid eye disease, what broad categories can cause orbitopathy?

Other causes of orbitopathy include orbital trauma, orbital inflammatory disease, and orbital tumors.

How can orbital trauma cause orbitopathy?

Orbital trauma can cause orbitopathy through extraocular muscle entrapment or orbital hemorrhage, leading to proptosis, motility restriction, diplopia, or acute orbital signs.

What inflammatory conditions can mimic or cause orbitopathy?

Inflammatory causes include orbital cellulitis, sarcoid or other autoimmune orbital inflammation, and idiopathic orbital inflammatory disease.

What should be considered in the differential diagnosis of proptosis or orbital signs?

The differential includes thyroid eye disease, carotid-cavernous fistula, trauma, orbital cellulitis/inflammation, sarcoid or autoimmune disease, idiopathic orbital inflammation, and orbital tumors.

What is the basic mechanism of myasthenia gravis?

Myasthenia gravis is caused by antibodies against the acetylcholine receptor at the neuromuscular junction, which disrupts normal neuromuscular transmission and causes fatigable weakness.

What are the classic ocular symptoms of myasthenia gravis?

The classic ocular symptoms are ptosis and diplopia, both of which typically worsen as the day progresses due to fatigability.

Why is ptosis high-yield in myasthenia gravis?

Ptosis is often an early clue to MG and is the first symptom in about 50% of patients. It is classically fatigable, worsening with sustained use or later in the day.

What systemic weakness symptoms can occur in myasthenia gravis?

MG can cause muscle group weakness, including difficulty walking, as well as weakness of pharyngeal muscles, which can cause voice changes.

What myasthenia gravis symptoms are potentially life-threatening?

Difficulty swallowing or breathing can be life-threatening because bulbar and respiratory muscle weakness may progress to myasthenic crisis.

What systemic symptoms should raise concern for generalized myasthenia gravis rather than isolated ocular MG?

Generalized MG is suggested by limb weakness, difficulty walking, voice changes, dysphagia, or dyspnea, especially when symptoms worsen with fatigue.

What eye movement abnormalities can occur in myasthenia gravis?

MG can cause variable ocular motility deficits, ranging from upgaze paresis to total ophthalmoplegia. It can mimic any cranial nerve palsy.

What bedside findings support ocular myasthenia gravis?

Findings include ptosis that worsens with extended upgaze, Cogan lid twitch, worsening diplopia with fatigue, and variable ocular motility deficits.

What is the Cogan lid twitch sign?

In Cogan lid twitch, the patient looks from downgaze to primary gaze, and the eyelid briefly overshoots or twitches upward before settling back into its usual position. It supports ocular MG.

What happens when the more ptotic lid is manually elevated in myasthenia gravis?

Manually elevating the more ptotic lid may cause the opposite lid to droop more, reflecting abnormal fatigable eyelid control in MG.

What eyelid muscle weakness can be seen in myasthenia gravis?

MG can cause lid weakness from impaired orbicularis oculi function, contributing to abnormal eyelid closure or fatigability.

What bedside tests can support a diagnosis of ocular myasthenia gravis?

Bedside tests include the ice test and rest test. In both, improvement of ptosis supports ocular MG because weakness improves when neuromuscular transmission is temporarily supported or fatigue is reduced.

How is the ice test performed in suspected ocular myasthenia gravis, and what is a positive result?

Place ice over the closed eyelids for 2 to 5 minutes. A positive test is improvement in ptosis, and sometimes improvement in extraocular muscle function.

How is the rest test used in ocular myasthenia gravis?

The patient rests with the eyes closed for a period of time. Improvement in ptosis afterward supports MG because the weakness is fatigable and improves with rest.

What diagnostic tests can confirm myasthenia gravis beyond bedside testing?

Confirmation can include acetylcholine receptor antibody testing and pharmacologic testing such as the Tensilon test. The key antibody target is the ACh receptor at the neuromuscular junction.

How do acetylcholinesterase inhibitors treat myasthenia gravis?

Acetylcholinesterase inhibitors, such as Mestinon/pyridostigmine, prevent acetylcholine breakdown so acetylcholine remains longer at the neuromuscular junction, improving muscle activation.

What are the major treatment categories for myasthenia gravis?

Treatment includes acetylcholinesterase inhibitors, corticosteroids, other immunosuppressants, and sometimes thymectomy.

What does a positive rest test demonstrate in ocular myasthenia gravis?

A positive rest test shows improvement of ptosis after eyelid rest, demonstrating the hallmark MG feature of fatigable weakness that improves with rest.

In the slide example, what happens after resting with the eyelids closed?

The patient initially has bilateral ptosis, worse on one side. After resting in a dimly lit room with eyelids gently closed for 20 minutes, both eyelids elevate and return closer to normal.

Why is improvement after rest high-yield for diagnosing ocular MG?

Ocular MG causes fluctuating, fatigable weakness. Improvement after rest helps distinguish MG from fixed structural causes of ptosis or ophthalmoplegia.