• When Is Diplopia a Sign of Something Dangerous?

    In your already overbooked clinic, evaluating patients who present with double vision may seem a daunting challenge. A succinct and systematic evaluation can help you efficiently differentiate between dangerous and benign causes of diplopia. These clinical pearls will help stratify your differential diagnosis and get your patients the help they need. 

    Is the diplopia monocular or binocular? Does it resolve with pinhole?

    Answering this question is paramount in the workup of diplopia. This is the first thing you should ask your patient and confirm yourself. Is the diplopia monocular or binocular? Double vision from ocular misalignment will only be present when both eyes are open (i.e., only under binocular conditions). Binocular diplopia can be concerning as it may reflect an underlying intracranial process. Monocular diplopia, on the other hand, persists when either eye is closed and is usually refractive in nature. Patients usually describe monocular diplopia as a crisp image associated with an overlapping shadowed image while binocular diplopia is described as two completely separated crisp images. Refractive diplopia often resolves with pinhole or blinking and the underlying cause (e.g., dry eye, refractive error, cataract or epiretinal membrane) should be addressed. 

    Speed of symptom progression

    Once you’ve determined that your patient’s diplopia is binocular, you’ll want to get a sense of how fast their symptoms are progressing and what other underlying conditions might be contributing. Does the patient have vasculopathic risk factors, a history of antecedent trauma, cancer, autoimmune disease or a history of strabismus? 

    As Alfredo Sadun, MD, says, “Severity and tempo equal urgency.” This adage is true for all things medicine. Symptoms that are severe and progress rapidly are more alarming than changes that are intermittent with little progression. Patients with benign conditions such as decompensated intermittent exotropia or sagging eye syndrome often report intermittent symptoms. Their ductions are full and they have no other localizing signs. On the hand, patients with strokes complain of sudden onset of symptoms. 

    Notable exceptions include patients with giant cell arteritis (GCA), who can present with transient diplopia. Patients above the age of 50 with transient diplopia and review of systems concerning for vasculitis should be evaluated for GCA. Additionally, patients with ocular myasthenia gravis often present with intermittent symptoms. As these patients are at risk for life-threatening myasthenic crisis (i.e., respiratory failure), a heightened sense of suspicion is needed (e.g., diplopia with moment-to-moment fluctuation, intermittent ptosis or symptoms worse with fatigue), and emergency room precautions should be discussed with the patient.  

    What is the saccadic velocity of the weak eye?

    Start by evaluating the patient’s ductions to look for limitations. When a duction deficit is noted, you’ll want to check the relative saccadic velocity of the problematic eye. Saccadic what? Bear with me! I promise this information is worth it. 

    Saccades are the fast movements that the eye performs to foveate a target. Saccadic velocities differ in neurogenic, restrictive or muscular causes of diplopia and thus are invaluable in stratifying your differential diagnosis.

    How to test saccades

    Ask the patient to shift their eyes back and forth from the left to right without moving their head or blinking. You can offer fingers as your fixation target. Looking at the bridge of the nose, you can judge the relative speed of each eye’s movement. You’ll need to hold the eyelids to assess vertical saccades.

    What am I seeing?

    Normal saccades: If the saccades are normal, a restrictive problem is likely — think of a dog tethered on a leash. A dog’s movement is restricted by the leash but the speed at which it runs towards you is not. Tethering of a medial rectus muscle from a medial wall fracture may restrict its movement but nothing is stopping it from relaxing and allowing the eye to abduct rapidly. Same thing for thyroid eye disease or tumor infiltration. 

    Slowed saccades: If the saccadic velocity of a muscle is slowed, a nerve problem should be suspected — like a car without enough gas. Cranial nerve six palsies (Video 1) have slowed abduction saccades, as do internuclear ophthalmoplegias (INOs; Video 2).

    Lightning-fast saccades that fatigue and become slowed: Weak muscles from diseases like myasthenia gravis and chronic progressive external ophthalmoplegia move lightning fast when rested and fatigue with use. You should be able to see this phenomenon on an exam. 

    Tricks: I use the slow-mo video mode on my cellphone to help me gauge a patient’s saccadic velocities. Check out this video of a cranial nerve six palsy and a bilateral INO.  

    Is the problem isolated? 

    Big deficits generally mean bad business. For this reason, after I’ve isolated the problem, I step back and look for other problems. For example, a cranial nerve 6 palsy in isolation in a patient with vasculopathic risk factors can probably be monitored. However, if the patient has a cranial nerve 6 palsy AND ptosis or anisocoria or facial numbness, the body is telling you that there’s a bigger problem that needs further workup. After your sensorimotor exam, take time to look for ptosis, check levator palpebrae function and check cranial nerve V and VII function. 

    Don’t forget to do a dilated exam. I distinctly remember a patient with an intermittent esotropia who I dilated to be complete and found subtle Paton’s folds around the optic disc, a sign of acquired disc edema. This finding switched my suspicion from myasthenia gravis to intracranial mass. Indeed, the patient had a grapefruit-sized meningioma!

    Don’t forget to check peripheral vision. Confrontational visual fields at a minimum should be performed in patients presenting with strabismus. I recommend doing them yourself. Why? Your brain uses your peripheral vision to coordinate eye movements and maintain fusion. Patients with limited peripheral vision, such as from homonymous hemianopias or bitemporal hemianopias, have limited input. This leads to so-called “slippage,” or hemi-field slide phenomenon. Imagine you are trying to overlay two identical images. You won’t perform this task well if you can’t see large parts of both images. Similarly, the brain doesn’t know how to coordinate eye movements with large field deficits and the eyes end up “slipping,” causing double vision. 

    What about isolated cranial nerve 3 palsies? Cranial nerve 3 palsies, even in isolation, always induce anxiety in the provider. Patients older than 55 with known vascular risk factors who present with an isolated COMPLETE cranial nerve 3 palsy that is pupil sparing in a reliable pupil without a history of cancer can be monitored.  Otherwise, these patients should be sent to the emergency room for urgent imaging (e.g., computed tomography angiography or magnetic resonance angiography) to rule out an aneurysm or stroke. Only after these conditions have been ruled out should you send the patient to neuro-ophthalmology. 

    How do I know if the cranial nerve 3 palsy is isolated? Here’s the last thing you need to know about cranial nerve 3 palsies … for now. In a complete cranial nerve 3 palsy, you’ll want to ask the patient to infraduct, preferably in adduction, to evaluate for cranial nerve 4 function (Video 4). If the eye incyclotorts, cranial nerve 4 is likely intact and you have an isolated cranial nerve 3 palsy. If it is not intact or if you detect multiple cranial neuropathies, neuro-imaging is required with attention paid to the cavernous sinus and orbital apex where the affected nerves travel in close proximity.

    Make sure to follow up

    Follow up is a critical point that can’t be emphasized enough. As Mark Borchert, MD, taught me, “Bad things get worse,” and you want to be there to catch them. I can’t tell you the countless times I diagnosed a patient with a cranial nerve 6 palsy whose diplopia resolved on follow-up 6 weeks later — because the patient developed ptosis and really had myasthenia gravis. Or another patient who came with normal imaging that I reviewed myself that I diagnosed with hypertensive cranial nerve 6 palsy who upon follow up developed concurrent cranial nerve 3, 4 and 5 palsies because they actually had lymphoma infiltrating their cavernous sinus. Following up with patients and tracking the evolution of a condition lets me assess the tempo of the condition and know if they are on the road to recovery. 

    Key Points

    Consider neuro-imaging or emergent lab work up if the binocular diplopia is 

    • rapidly progressive
    • not isolated (multiple cranial nerve palsies)
    • incomplete pupil-sparing cranial nerve 3 palsy
    • occurs in association with a review of systems suggestive of GCA

    Tip: When you send your patients to the emergency room, be sure to send them with your note in hand so that they can communicate to the emergency department providers your concerns and recommendations.

    The Academy’s YO Info Editorial Board is collaborating with YO leaders from our subspecialty society partners and thanks the North American Neuro-Ophthalmology Society YONO Chair Collin McClelland, MD, for suggesting Kimberly Gokoffski, MD, to author this article.

    About the author: Kimberly Gokoffski, MD, PhD, is a clinician scientist and neuro-ophthalmologist at the University of Southern California Roski Eye Institute. She completed her residency training in ophthalmology at the University of California, Davis, followed by a fellowship in neuro-ophthalmology at USC. In addition to her clinical and surgical practice, Dr. Gokoffski directs a research group whose goal is to develop electric field application into a technology to assist with optic nerve regeneration.