Neuro-ophthalmology: Pupils, Diplopia & Visual Fields

The Pupil Examination

Relative afferent pupillary defect (RAPD). In the swinging-flashlight test, light is moved briskly between the eyes. When it reaches an eye with a damaged optic nerve, less signal reaches the midbrain and both pupils dilate (Marcus Gunn pupil). An RAPD marks optic neuropathy (optic neuritis, ischemic optic neuropathy, compression) or extensive retinal disease. Cataract and refractive error do not cause one, and because both pupils share the midbrain input, an afferent defect never produces anisocoria.

Anisocoria. Compare the pupils in dim and bright light. If the difference is greater in the dark, the small pupil cannot dilate and the lesion is sympathetic (Horner syndrome). If it is greater in bright light, the large pupil cannot constrict and the lesion is parasympathetic: CN III palsy, Adie pupil, or pharmacologic blockade. Physiologic anisocoria is less than 1 mm and the same in light and dark.

Light-near dissociation. Better constriction to a near target than to light points to three lesions. The benign Adie tonic pupil, usually in a young woman, follows ciliary ganglion damage; denervation supersensitivity makes it constrict to dilute (0.1%) pilocarpine, and with depressed tendon reflexes it is Holmes-Adie syndrome. Argyll Robertson pupils indicate neurosyphilis (diabetes can mimic them). Dorsal midbrain (Parinaud) lesions give light-near dissociation with mid-dilated pupils.

Horner Syndrome

The triad. Loss of oculosympathetic tone produces mild (1–2 mm) upper-lid ptosis from Müller muscle weakness, a small pupil that dilates slowly in the dark (dilation lag), and facial anhidrosis. Confirm with apraclonidine: denervated α1 receptors become supersensitive, so its weak α1 effect dilates only the Horner pupil and reverses the anisocoria. The older cocaine test works the other way: the normal pupil dilates and the Horner pupil does not.

Localizing the lesion. The pathway has three neurons:

• First-order (central): hypothalamus through the brainstem to the C8–T2 cord; lateral medullary stroke, syrinx, and cord lesions, usually with other brainstem or cord signs.
• Second-order (preganglionic): from the cord over the lung apex to the superior cervical ganglion; Pancoast tumor, neck or chest surgery, central lines, and trauma.
• Third-order (postganglionic): along the internal carotid into the cavernous sinus; carotid dissection, cavernous sinus lesions, and cluster headache. Facial sweating fibers leave with the external carotid, so these lesions largely spare facial sweating.

Painful acute Horner syndrome, with neck, face, or head pain, is internal carotid dissection until proven otherwise: obtain CTA or MRA of the head and neck emergently, because stroke risk is highest early.

Other urgent patterns. Horner syndrome with shoulder and medial arm pain and weak hand muscles in a smoker points to a Pancoast tumor invading the lower brachial plexus (C8–T1) and sympathetic chain; image the chest with CT. A lighter iris on the affected side implies a congenital Horner syndrome, and a new Horner syndrome in a young child warrants evaluation for neuroblastoma. In every unexplained case, imaging should cover the carotid and the lung apex.

Diplopia and Ocular Motor Palsies

Monocular or binocular. Diplopia that disappears when either eye is covered is binocular and reflects misalignment: a cranial nerve palsy, INO, neuromuscular junction disease, or orbital disease. Diplopia that persists with the other eye covered is monocular and ocular in origin (refractive error, cataract, dry eye, corneal disease) and needs an eye examination, not neuroimaging. Next establish whether images are separated horizontally or vertically and in which direction of gaze the separation is worst.

Third-nerve palsy. A complete CN III palsy causes ptosis and an eye resting down and out. The pupillomotor fibers run on the surface of the nerve, so compression dilates the pupil early. A dilated, unreactive pupil, especially with headache, means a posterior communicating artery aneurysm until proven otherwise: obtain emergent CTA (or MRA or catheter angiography); in a comatose patient it signals uncal herniation. Ischemia from diabetes or hypertension infarcts the nerve's core and spares the pupil; such palsies are often painful and usually recover within about 3 months. Control vascular risk and follow closely, imaging if the pupil becomes involved, the palsy is incomplete, other deficits appear, or recovery fails.

Fourth-nerve palsy. Superior oblique weakness leaves the affected eye higher (hypertropia), with vertical diplopia worst when looking down and inward, as when reading or descending stairs. Patients tilt the head away from the lesion to offset lost intorsion. Trauma is the most common acquired cause because the nerve is long and thin and is the only one to exit the dorsal brainstem; decompensation of a congenital palsy is another.

Sixth-nerve palsy. Lateral rectus weakness produces esotropia and horizontal diplopia worse at distance and on gaze toward the lesion. The long course over the petrous apex makes CN VI a false-localizing sign of raised intracranial pressure (tumor, idiopathic intracranial hypertension, venous sinus thrombosis) or of low pressure after lumbar puncture. Microvascular ischemia and Wernicke encephalopathy are other causes. Gradenigo syndrome combines CN VI palsy, retro-orbital pain, and ear discharge from petrous apicitis complicating otitis media.

Internuclear ophthalmoplegia (INO). A lesion of the medial longitudinal fasciculus (MLF) disconnects the abducens nucleus from the opposite oculomotor nucleus. On lateral gaze the eye on the side of the lesion fails to adduct while the abducting eye shows nystagmus; convergence is preserved, proving CN III and the medial rectus work. Bilateral INO in a young adult suggests multiple sclerosis; unilateral INO in an older adult suggests brainstem stroke. Myasthenia gravis can mimic INO, but it fluctuates and usually causes ptosis.

Parinaud (dorsal midbrain) syndrome. Compression of the dorsal midbrain causes upgaze palsy, mid-dilated pupils with light-near dissociation, convergence-retraction nystagmus on attempted upgaze, and eyelid retraction (Collier sign). Causes include pineal tumors (germinoma in young males), obstructive hydrocephalus (the "setting-sun" sign in infants), midbrain stroke, and multiple sclerosis.

Visual Field Defects

Localizing principle. A defect confined to one eye lies in the retina or optic nerve of that eye and often brings an RAPD. A bitemporal defect localizes to the chiasm, where the crossing nasal fibers serving both temporal fields meet. Homonymous defects lie behind the chiasm on the opposite side, and they become more congruous (identical in both eyes) the farther back the lesion sits.

Chiasmal compression. A pituitary macroadenoma presses on the chiasm from below, so the inferior crossing fibers, which serve the superior temporal fields, fail first. A craniopharyngioma, often a calcified suprasellar cyst in a child (with a second peak in older adults), presses from above and removes the inferior temporal quadrants first; it may also cause growth failure and diabetes insipidus. The workup is pituitary MRI with contrast, formal visual fields, and pituitary hormone testing.

Retrochiasmal lesions. Meyer loop, the inferior optic radiation fibers, sweeps through the temporal lobe, so temporal lesions cause a contralateral superior quadrantanopia ("pie in the sky") and parietal lesions a contralateral inferior quadrantanopia ("pie on the floor"). A PCA-territory occipital infarct spares the macula because the occipital pole also receives MCA collateral flow; patients bump into objects on the blind side, typically without weakness.

Papilledema

Definition and clues. Papilledema is bilateral optic disc swelling caused by raised intracranial pressure. Patients report headache worse lying down or on waking, transient visual obscurations when standing, and pulsatile tinnitus; a CN VI palsy may be present. Visual acuity is preserved early while the blind spot enlarges; untreated, peripheral field loss follows.

Image before any lumbar puncture: urgent MRI with MR venography excludes a mass and cerebral venous sinus thrombosis. Only then is opening pressure measured; normal imaging with high pressure supports idiopathic intracranial hypertension, treated with weight loss and acetazolamide.

Unilateral disc swelling with sudden or painful vision loss and an RAPD is an optic neuropathy (optic neuritis or ischemic optic neuropathy), not papilledema.