Recently, I was asked to watch after someone’s dog for a week. I’m a dog guy, and I’ve had dogs since I could stand on my own two feet. So I agreed, much to my fiance’s dismay. A Yorkshire terrier named Coco who wasn’t perfectly house
trained, who wasn’t the most steady on her feet, and who may or may not have had the worst acid reflux I’ve seen in a dog. We were stuck with her for an entire week, and I don’t think Erika will ever forgive me for it. I only bring up the story of Coco because, in spite of all of her other medical problems, I noticed something else about her while we took care of her. She had grossly asymmetric pupils. The left pupil was much larger than the right pupil. It reacted much more slowly and less fully to light. And this difference in pupil size was greater in bright light than dim light. You might know what is wrong with Coco at this point, but I’ll give you my thoughts at the conclusion of this episode after Dr. Ali Hamedani shares with us his approach to a patient with anisocoria.
Ali opens the interview by discussing mechanical or structural disease of the eye which can cause anisocoria. These are diagnoses an ophthalmologist will easily recognize, and ones (I believe) a neurologist will easily neglect. So they are important to acknowledge a few of the major players here: iris trauma, iris or uveitis, scarring from prior ocular surgery, colobomas or core ectopias (displacement of the cornea). From there, Ali moves on to the neurologic evaluation of anisocoria. The flowchart from Dr. Liu’s textbook on Neuro-Ophthalmology is below:
For the sake of space, I am going to summarize several of the classic unilateral pupillary abnormalities according to size and list them. I’d recommend you listen to Ali’s full explanation in the show.
THE ABNORMALLY LARGE, ASYMMETRIC PUPIL
- Physiologic anisocoria – Sometimes one pupil is just a little larger than the other. How you distinguish this from more concerning pupillary abnormalities is that each pupil will constrict equally to light and dilate equally to dark.
- Adie’s Tonic pupil – A disorder of the ciliary ganglion resulting in mydriasis and sluggishly reactive pupils, more common in a young patient (F:M 3:1) with a large pupil. Can have a sectoral component to it, with some segments of the pupil constricting more than others. It is one diagnosis of several when you are evaluating a patient with light-near dissociation.
- Pharmacologic pupil – Often caused by recent anti-cholinergic exposure, topical or oral or inhaled. So a patient coming back from a trip with a scopolamine patch, or a patient in the ICU who received nebulized ipratropium.
- Third nerve palsy – Can be total (with levator palpebrae, SR, IR, MR, and IO impairment), or an inferior divisional IIIrd nerve palsy (with impairment of IR, IO, and MR). Your first step here, after confirming it is not a skew or other ocular motor palsy, is to identify if it is pupil-sparing or pupil-involving. A pupil-sparing oculomotor palsy indicates damage intrinsic to the nerve–such as a vascular IIIrd nerve palsy–whereas abnormal dilation of the pupil with or without oculomotor deficits may be more indicative of a compressive lesion–such as an aneurysm of the posterior communicating artery or a tumor. You also see “third nerve palsy” syndromes in other conditions such as uncal herniation, which is why a lot of providers tend to panic when they see a new oculomotor palsy.
THE ABNORMALLY TINY, ASYMMETRIC PUPIL
- Horner’s Syndrome – Characterized by loss of sympathetic input from the superior cervical ganglia, so symptoms as you would expect:
- Partial ptosis
- +/- Enophthalmos
Common causes of a Horner’s Syndrome in the adult patient. From Liu et al, Neuro-ophthalmology. 2010.The trick about Horner’s Syndrome is that the sympathetic input to the eye is a lengthy pathway, originating from the hypothalamus, with fibers descending through the brainstem and synapsing on the intermedolateral cell column around C7-T1, deploying fibers out toward the superior cervical ganglia, and then reascending to the orbit via the internal carotid/ophthalmic arteries.
Drop tests. There’s much to be said about how eye drops and other examination maneuvers can be used as aids in your differential diagnosis. Take a case of Horner’s Syndrome, for example. Most people just image the entire sympathetic pathway anyway, but it’s kind of interesting to know. So, by giving a patient 0.5% topical apraclonidine to both eyes, the affected eye by the Horner’s Syndrome will dilate to a much greater size than the contralateral pupil. This is due to subacute (>48hours) or chronic denervation of that eye leading to overexpression of alpha adrenergic receptors and hypersensitivity of that pupil to sympathetic stimulation. This confirms the Horner’s, but won’t tell you where the lesion is. Next, you administer hydroxyamphetamine, which stimulates release of norepinephrine from the intact post-ganglionic neuron (3rd order neuron in the 3-neuron Horner pathway). If the affected pupil also dilates in response to these eye drops, then the 3rd order neuron is alive and thus the disease must be affecting the 1st or 2nd order neuron. If there is no dilation of the pupil, then the hydroxyamphetamine could not have stimulated release of norepinephrine because there was none to release–that nerve is dead. 🙁
So back to Coco… Remember that dog we talked about at the beginning of the show? When Ali did his much more thorough eye exam on Coco, he was able to quickly tell she had an exophoria in nearly all directions of gaze—meaning her ocular alignment was impaired. The left eye (the affected eye) was looking too far to the left. And Ali confirmed this with pupillary transillumination. That’s the fancy description for, he shined his iPhone light into Coco’s eyes and saw the bright point of his light reflect off different areas of her pupils. This confirmed the exophoria.
Together with the fact that her left pupil was larger than the right, it was less reactive to light, and the anisocoria was worse in brighter ambient light than in darkness, was indicative that she has a pupil-involving third nerve palsy. Given the lack of ptosis, this might be an inferior divisional oculomotor nerve palsy—because, as Ali mentioned, the superior division innervates the superior rectus and levator palpebrae muscles while the inferior division supplies everything else, including the parasympathetic fibers. For more information on disorders of ocular alignment, check out Ali’s earlier episode on painless ophthalmoparesis, episode number 9.
BrainWaves podcasts and online content are intended for medical education purposes only and should not be used for routine clinical decision making, no matter how physiologic you think those pupils are.
- Liu GT, Volpe NJ, and Galetta SL. Neuro-ophthalmology: Diagnosis and management, 2nd ed., pp. 587-610. Elsevier, 2010.