Let's Talk LMCC
Diplopia

RCB [00:00:07]: Hello, my name is Renée-Claude Bider, and I'm a podcast associate with the McGill Journal of Medicine. Welcome to Let's Talk LMCC. Today's episode was written by Jenna Kliot, who will be hosting with expert advisor Dr. Fraser Moore. Jenna is a third-year Medical Student here at McGill and is currently researching single-fiber EMG testing in the diagnosis of myasthenia gravis.
In addition to his work as a clinician, Dr. Moore is an Associate Professor in the Department of Neurology and Neurosurgery, an Associate Member of the McGill Institute of Health Science Education, and a Program Director for the McGill Adult Neurology Residency Program.
In this Episode, you'll be hearing Dr. Moore ask Jenna questions about diplopia, covering differential diagnosis, key findings, critical investigations, and management. Here's the Episode.
FM [00:00:54]: Well, Jenna, maybe you can begin by explaining “what is diplopia?”
JK [00:00:59]: Diplopia, or double vision, refers to seeing two images of the same object at the same time.
FM [00:01:05]: And what is your initial approach to diplopia?
JK [00:01:08]: When we first see a case of diplopia, it's important to distinguish between monocular and binocular diplopia. Monocular diplopia is double vision when looking with one eye, whereas binocular diplopia is double vision when looking with both eyes. Patients will not always know whether one or both eyes is affected, so it's best to have them cover one eye at a time and see when the diplopia is present. It also is important to ascertain whether the double vision is horizontal or vertical. Are the images next to each other, on top of each other, or oblique?
FM [00:01:46]: What is the difference in pathophysiology between monocular and binocular diplopia?
JK [00:01:53]: Monocular diplopia occurs due to a pathology within the eye, which results from abnormalities in the optical media that affect the eye's ability to properly project images onto the retina. These refractive errors can be caused by lens displacement, particular corneal irregularities, or astigmatism. On the other hand, binocular diplopia arises from a misalignment or lack of synchronization between the eyes. As a rough rule of thumb, monocular diplopia is managed by an ophthalmologist, while binocular diplopia is managed by neurology, ophthalmology, or both, depending on the cause.
FM [00:02:34]: How would you take a good history for a person with diplopia?
JK [00:02:38]: When taking a patient's history, it's crucial to get a detailed description of their diplopia. Start by understanding when it began, did it develop gradually or come on suddenly? It's also important to determine whether the diplopia occurs in all directions of gaze or only when the patient looks in certain directions. Ask if the diplopia is constant throughout the day or if it appears in specific situations or at specific times. Be sure to inquire about whether the images are separated vertically or horizontally, and if certain head positions, like tilting, affect the severity of the double vision. Finally, ask if the diplopia is associated with pain and whether the pain is constant or only occurs in particular positions of gaze. Besides understanding the diplopia, a thorough general history, including a review of systems, medical and surgical history, will help lead you to a diagnosis. Pay close attention to symptoms of hyperthyroidism, vascular risk factors, and previous ophthalmic surgeries.
FM [00:03:44]: Before we get into a bit more detail about the approach to binocular diplopia, what anatomy is important for everyone to know?
JK [00:03:52]: The eye is controlled by six extraocular muscles: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique, and inferior oblique. Each rectus muscle moves the eye in the direction implied by its name, such as the superior rectus elevating the eye and the lateral rectus abducting it. In contrast, the oblique muscles perform movements opposite to what their names suggest; the superior oblique causes depression, while the inferior oblique causes elevation. The superior and inferior obliques are the primary muscles responsible for intorsion and extorsion, respectively. The rectus muscles also contribute to intorsion and extorsion, but not as significantly. It's important to note that certain combinations of extraocular muscles are always active, even when the eyes aren't moving. This makes it possible to keep the eye in a given position of gaze. These muscles are innervated by cranial nerve three (oculomotor), cranial nerve four (trochlear), and cranial nerve six (abducens). The trochlear nerve innervates the superior oblique, which passes through the trochlea. The abducens nerve innervates the lateral rectus, which abducts the eye. And the remaining muscles are innervated by the oculomotor nerve. The oculomotor nerve also innervates the levator palpebrae superioris, which elevates the eyelid and contains parasympathetic fibers which are responsible for constriction of the pupils. Lastly, it's important to understand the role of supranuclear pathways, which provide the commands to the cranial nerves that, in turn, control the eye muscles. These pathways act as the brain's input system, ensuring coordinated eye movements by transmitting the necessary instructions to the muscles.
FM [00:05:51]: Ok, now that we know the anatomy, what is the approach to localizing the problem?
JK [00:05:57]: This is where a good physical exam comes into play. When a patient presents with binocular diplopia, a full neurological exam is indicated. Before beginning the ocular exam, observe the position of the eyelids. Ptosis could imply the involvement of levator palpebrae superioris, which is common in myasthenia gravis or a cranial nerve III palsy. A retracted eyelid could suggest Graves’ orbitopathy. All of these pathologies will be discussed later in the podcast. Next, pay particular attention to the position of the eyes in primary gaze. If the nerve palsy is severe or complete, one could see an abnormality in primary position. For example, in a complete cranial nerve three palsy, you would expect the eye to be abducted and looking downwards with ptosis and mydriasis. If a nerve palsy is not as severe, an abnormality in primary gaze is not always present and may only be seen during extraocular movements. If this is the case, the diploma is likely only present in the specific positions of gaze in which the ocular movements are not full. For example, in a partial cranial nerve six palsy, a limitation in abduction could be observed, and horizontal diplopia on abduction would be expected. After primary position, including eyelid position and extraocular movements are examined, it is time to observe the pupillary response. A mydriatic large pupil suggests a cranial nerve III involvement. Remember, the parasympathetic fibers responsible for constriction of the pupil travel with cranial nerve III. Fundoscopy is also indicated, as a swollen disc suggests increased intracranial pressure. Optic disk edema is a late finding of increased intracranial pressure and is a red flag for tumors and other compressive pathologies. Any other abnormalities in the remainder of the cranial nerve and neurological exam would point to a more diffuse disease process, such as multiple sclerosis or numerous ischemic events, both of which will be discussed later.
FM [00:08:03]: Thank you for that overview of the general physical exam. Are there any special tests to do on exam if you expect specific pathologies?
JK [00:08:12]: Yes, in fact, if you are considering myasthenia gravis in your differential testing for fatiguability and an ice pack test should be performed. When assessing for fatiguability, have the patient look up for one minute; if the diplopia or ptosis worsens, it is suggestive of myasthenia gravis or other neuromuscular junction disease. The ice pack test is used in a patient with ptosis whom you suspect myasthenia. You would put an ice pack on the affected eye for five to seven minutes and reexamine the eyelid of the patient. If the ptosis is less severe, that is a positive result favoring a diagnosis of myasthenia.
FM [00:08:23]: Now that we know how to localize lesions and take a targeted history, how can we categorize and diagnose specific etiologies?
JK [00:09:03]: One way that we can categorize binocular diplopia is by dividing ideologies into two categories, paralytic and compressive. In the paralytic category, we have myasthenia gravis, multiple sclerosis, compressive lesions, ischemic lesions, temporal arteritis, and diabetic neuropathies. In the restrictive category, we have thyroid eye disease, orbital cellulitis, and traumatic floor fractures.
FM [00:09:30]: Wow, that is a lot of etiologies. Starting with the restrictive lesions, let's go through them one by one. What is your approach to thyroid eye disease?
JK [00:09:39]: Thyroid eye disease is an ocular manifestation of Graves’ disease, which is an autoimmune condition where the thyroid-stimulating hormone receptor antibodies, known as TRAbs, are produced. Fibroid-stimulating hormone receptor is expressed in the thyroid but also in various tissues, including fibroblasts and adipocytes in the orbits of the eye. These cells get stimulated by the autoantibodies in Graves’ and increase the volume of the extraocular muscles and soft tissue, and causes inflammation. This inflammation pushes the eyeball forward, leading to compression of the extraocular muscles and impaired venous drainage, leading to even more swelling. The classical presentation of thyroid eye disease is bilateral proptosis with symmetrical lid retraction and diplopia. Diplopia is first present in extremes of gaze, but as the disease progresses, it can start to affect closer and closer to primary gaze. It can, but does not have to be, associated with other symptoms of hyperthyroid disease. When you suspect thyroid eye disease, it is important to order Labs for TSH, TRAbs T3, and Free T4. On physical exam, you could see periorbital edema, conjunctival erythema, proptosis, lid retraction, and a limitation of extraocular movements. Visual acuity, visual fields, color vision, and optic discs should also be assessed, as they can be affected in severe cases where the optic nerve is involved. Non-contrast MRI or CT can also be ordered in moderate to severe cases to assess involvement of the optic nerve. Consult ophthalmology and endocrinology urgently if there is optic nerve involvement.
FM [00:11:27]: Great. How about orbital cellulitis?
JK [00:11:31]; Orbital cellulitis is a soft tissue infection of the area around the extraocular muscles and often manifests as painful extraocular movements, swelling and erythema of the eyelids, diplopia in certain positions of gaze, and is associated with sinusitis and fever. Decreased color vision and relative afferent pupillary defects in these patients are indications of optic nerve involvement and are cause for concern. Patients with orbital cellulitis will need IV antibiotics and a CT Head, and may or may not need surgical drainage if the imaging reveals a drainable abscess. If you suspect orbital cellulitis, prompt referral to ophthalmology is indicated.
FM [00:12:17]: So far, we've discussed thyroid orbitopathy and orbital cellulitis. The last compressive cause of binocular diplopia on our list is orbital floor fracture. What is your approach to this?
JK [00:12:32]: A traumatic orbital floor fracture is an easy-to-identify cause of binocular diplopia, as it follows a high-impact trauma. In some cases of orbital floor fracture, the inferior rectus muscles can be entrapped, impairing down gaze and causing a horizontal diplopia. Nausea and vomiting can be associated with inferior rectus entrapment. A facial trauma with diplopia, with or without nausea and vomiting, warrants a CT Head and an urgent ophthalmology consultation. One type of orbital floor fracture that is often missed is the white eyed orbital blowout. This is most commonly seen in children but is a type of orbital fracture that presents with restriction in ocular motility with minimal to no soft tissue trauma. This emergency can be difficult to diagnose due to the lack of soft tissue, swelling, or erythema, and should always be on your radar when a patient presents with diplopia following a head trauma. This type of injury is particularly dangerous as it can induce the oculocardiac reflex, which can cause bradycardia, headache, and malaise.
FM [00:13:45]: Great. Thanks for the recap of compressive causes of binocular diplopia. Now we can start to go over the paralytic causes. These include myasthenia gravis, multiple sclerosis, intracranial compressive lesions, ischemic lesions, temporal arteritis, and diabetic neuropathies. Let's start with myasthenia gravis. Can you explain what it is?
JK [00:14:12]: Myasthenia gravis is an autoimmune condition where the body produces antibodies against the acetylcholine receptors at the neuromuscular junction, reducing the number of functioning acetylcholine receptors. The amount of acetylcholine released with each action potential decreases with each repeat, and with less functioning acetylcholine receptors, repeat action potentials do not have enough acetylcholine needed to overcome the decreased number of receptors. This means that consecutive repeating action potentials do not all result in muscle cell depolarization and contraction. Because acetylcholine receptors are present at all neuromuscular junctions, any skeletal muscle can be affected. Extraocular muscles are most commonly involved, but bulbar limb and diaphragm muscles can also be as well. The classical manifestation of ocular myasthenia gravis are diplopia and/or ptosis, which fluctuate and are worse at the end of the day. They improve with rest or cold temperature and worsen with movement. Bulbar involvement causes dysphagia or coughing late in meals, while limb involvement manifests as proximal, fatigable limb weakness. Diaphragmatic involvement leads to life-threatening dyspnea requiring mechanical ventilation. When you suspect myasthenia gravis clinically, order serology for acetylcholine esterase antibodies and a single fiber EMG. Diagnosis of myasthenia gravis is based on test results and clinical presentation. If suspected, consult neurology. In the treatment of myasthenia gravis, acetylcholine esterase inhibitors are first-line, but systemic steroids and IVIG can be added depending on the severity of the disease and the response to treatment. In purely ocular myasthenia gravis, the treatment is for symptomatic relief and has no disease-modifying properties. In a myasthenic crisis or in a patient with bulbar involvement, the treatment is more important as swallowing and respiration are essential bodily functions.
FM [00:16:33]: How does this differ from the presentation of multiple sclerosis, another autoimmune cause of binocular diplopia?
JK [00:16:41]: Multiple sclerosis, or MS, is an autoimmune attack of the myelin sheath, which surrounds the axons in the central nervous system. It usually presents in young adults in one or more distinct episodes of focal central nervous system dysfunction. The symptoms worsen over hours to days and then gradually improve over weeks to months. They often do not heal completely. One very common manifestation of MS is optic neuritis, but any part of the central nervous system can be attacked, including the brainstem and cranial nerves. When cranial nerves three, four, or six are affected, a limitation of extraocular movements is produced, which is what causes the diplopia. With MS-induced diplopia, there may be other neurological deficits occurring either at the same time or historically. MS is managed by a neurologist in conjunction with ophthalmology if there is ocular involvement. MS is treated with systemic steroids during an acute flare-up and immunomodulatory therapies long-term. Prompt MS diagnosis is essential as early initiation of immunomodulatory therapies is associated with less disability later in life, as disability from each flare-up can accumulate.
FM [00:18:12]: Now that the autoimmune causes are covered, what are some types of lesions which can cause paralytic diplopia?
JK [00:18:19]: Aneurysms and tumors can both compress cranial nerves, leading to a paralytic diplopia. They are difficult to diagnose based on physical exam alone, and if they are suspected, imaging is required. This could include a CT or MRI of the Head for tumors or a CT angiogram for an aneurysm. Aneurysms can be treated surgically with clipping or coiling, and tumors can be treated with radiotherapy, chemotherapy, and/or surgery, depending on their susceptibility and location. Both lesions require a consult to neurosurgery.
FM [00:18:59]: How about ischemic legions? Are we able to differentiate them from compressive lesions clinically?
JK [00:19:06]: Well, it depends. Sometimes imaging is necessary to tell the two apart, but with good knowledge of anatomy, there are some situations where you can tell the difference clinically. As we discussed earlier, cranial nerve three contains both motor and parasympathetic fibers. The parasympathetic fibers are located on the outside of the nerve and will be the first to be affected in a compressive lesion, like a tumor or an aneurysm. Contrarily, the motor fibers run inside the nerve and will be the first to be affected in an ischemic lesion, so a blown pupil with some ocular motor limitations is suggestive of compression, whereas a large limitation in extraocular movements without pupillary involvement is suggestive of ischemia. As a simple rule, if the pupil is normal but all the other functions of cranial nerve three are completely absent, then this suggests an ischemic lesion, and imaging is not necessary. For all other combinations of symptoms, imaging is necessary.
FM [00:20:17]: How about temporal arteritis? How could it present?
JK [00:20:22]: Temporal arteritis, also known as giant cell arteritis, is an autoimmune vasculitis common in older people. It usually presents with a headache, scalp tenderness, jaw claudication, and loss of vision with absent or asymmetric temporal pulses on physical exam. However, in rare cases, it can also present with diplopia from cranial nerve palsies. If you suspect a temporal arteritis, systemic corticosteroids and an immediate rheumatology consult are necessary since it can cause irreversible blindness.
FM [00:21:03]: Lastly, in the paralytic category, we have diabetic mononeuropathy. How can it present?
JK [00:21:11]: Diabetic patients can get self-limited, painful cranial mononeuropathies. The pathophysiology is similar to other diabetic nerve damage, which is damage to blood vessels supplying the nerves from hyperglycemia and insulin resistance. The most common one is cranial nerve three, and it typically presents as a few days of unilateral pain around the orbit, followed by the onset of a cranial nerve three palsy. It is important to note that the pupillary response to light can be preserved in diabetic cranial nerve three palsy, as with ischemic lesions discussed earlier. Diabetic cranial nerve three palsy generally resolves after three months without any treatment, so watchful waiting is the main management plan. Diabetic cranial mononeuropathies can also affect the fourth or sixth nerve. Imaging is usually indicated even if diabetes is suspected as the cause of the third, fourth or sixth nerve lesion, even though they all resolve without treatment. This is because it is difficult to rule out other, more worrisome causes. The one exception would be a pupil-sparing cranial nerve three lesion as discussed previously.
FM [00:22:34]: Thanks for that recap of all the paralytic and compressive causes of binocular diplopia. There's just one case left to discuss. What if a patient presents with binocular diplopia but has no abnormalities of extraocular movements?
JK [00:22:51]: A presentation like this is suggestive of a decompensation of a long-standing strabismus. Strabismus means ocular misalignment and can be congenital or acquired. When a patient presents with painless binocular diplopia with no extraocular movement abnormalities, we can do some special tests to try and elicit the misalignment: the cover-uncover test and alternate-cover test. The cover-uncover test involves having the patient focus on a specific object in the distance with both eyes. Then, one eye is covered with an opaque object. If the uncovered eye moves to focus on the object as the other eye is being covered, that is a positive result. If the uncovered eye does not move, the test is negative. A positive result suggests strabismus and merits an ophthalmology consult.
FM [00:23:53]: Great, now that we have covered all the material, let's try some practice LMCC-style questions. First question: A twenty-year-old construction worker presents to your clinic with double vision. He explains that he was hit in the face by a metal beam at work, and despite having minimal swelling, is seeing double, has been vomiting, and having fainting spells since the injury. On exam he has extreme right periorbital tenderness and limited depression of the right eye with vertical binocular diplopia present on downgaze. What is the best management for this patient? 1. An outpatient neurology consultation; 2. An urgent neurology consultation; 3. An outpatient ophthalmology consultation. Or [4.]: An urgent ophthalmology consultation.
JK [00:25:05]: The correct answer is urgent ophthalmology consultation. This is likely a white eyed orbital blowout fracture and is a surgical emergency. The indicators include trauma, syncope suggesting oculocardiac reflex involvement, and limited down gaze, which points to inferior rectus entrapment.
FM [00:25:30]: A 76-year-old woman presents to the clinic with double vision. She explains that she only notices it in extremes of gaze, and she isn't quite sure when it started. She complained of some discomfort, but no pain. On exam you notice some proptosis limitation of extraocular movements in all extremes of gaze and lid retraction. What is your most likely diagnosis? 1. Myasthenia gravis; 2. Orbital cellulitis; 3. Graves’ orbitopathy; 4. Temporal Arteritis.
JK [00:26:14]: Graves’ Orbiopathy is the correct answer. Proptosis, lid retraction, and diplopia in all extremes of gaze are clues that suggest this diagnosis. Orbital cellulitis could also present with proptosis, but it is usually unilateral, painful, more acute in onset, and associated with infectious symptoms. Temporal arteritis would be very painful and would not cause proptosis or lid retraction. Myasthenia gravis would not present with lid retraction. It could have ptosis, and it would not have proptosis and is fatigable.
FM [00:26:57]: A 64-year-old man known for hypertension and diabetes presents to your Clinic with double vision. He tells you that last week he had severe pain around his left eye, and today he started noticing double vision. You examine him and note a limitation in abduction of the left eye with binocular diplopia on left gaze. There are no other neurological deficits on exam. What is the best course of action? 1. Watchful waiting; 2. Dual antiplatelet therapy for two weeks, and then aspirin for life; 3. Aspirin only; 4. CT scan of the head.
JK [00:27:47]: The correct answer is CT Head. Even though this is most likely a diabetic sixth nerve palsy, given the involvement of only the lateral rectus muscle, we cannot confidently rule out compressive etiology without imaging. We would not start any medication before the CT since diabetic cranial neuropathies are self-limited without treatment, and this is still the most likely diagnosis. The clues for this diagnosis are the pain preceding the diplopia and the diabetes on history.
JK [00:28:23]: So, to summarize, we discussed a practical approach to diplopia. We discussed relevant points on history taking and how to localize the problem on physical exam. We then distinguished monocular and binocular diplopia. Monocular diplopia is caused by an intraocular problem and warrants an ophthalmology referral. We divided binocular diplopia into two categories: restrictive and paralytic causes. In the restrictive category, we discussed thyroid orbitopathy, orbital cellulitis, and orbital floor fractures. Remember, any optic disc edema or optic nerve involvement is an emergency, and an urgent ophthalmology consult is needed. In the paralytic category, we discussed myasthenia gravis, multiple sclerosis, compressive nerve lesions like tumors and aneurysms, ischemic nerve lesions, temporal arteritis, and diabetic cranial neuropathies. Remember that fatigable diplopia is suggestive of myasthenia gravis, and diplopia with other focal neurological deficits is suggestive of multiple sclerosis. Review the anatomy to localize a nerve lesion. Imaging is almost always indicated to find out its etiology. Remember, pupillary involvement is a great clue. Lastly, we covered strabismus. Although rare, it should still be included in your differential diagnosis. Thank you for listening, and good luck studying.
RCB [00:30:10]: We hope you enjoyed this episode, and thank you again to Jenna Jiliot and Dr. Fraser Moore for their contribution. For details about the LMCC objectives, other resources, and information about our expert advisor, please check out the episode description below. If you're interested in writing or hosting an episode of Let's Talk LMCC, please reach out to us by email at mcgilljmed.podcast@gmail.com, and as always, as this is a podcast made in the spirit of learning, we would love to hear your feedback. Stay tuned for our next episode.