Anisocoria: Horner syndrome, Adie tonic pupil and third nerve palsy
Quick answer
Anisocoria means the pupils are unequal in size. The key first step is to compare them in bright light and in dim light. If the difference is greater in the dark, the smaller pupil is abnormal because it cannot dilate — think Horner syndrome. If the difference is greater in bright light, the larger pupil is abnormal because it cannot constrict — think third nerve palsy, Adie tonic pupil or a pharmacologically dilated pupil. A difference of about 1 mm or less that is the same in light and dark is usually physiological.
Open the simulatorA step-by-step approach to unequal pupils
- Measure both pupils in bright light and in dim light while the patient looks at a distant target.
- Decide which pupil is abnormal: anisocoria greater in the dark → the small pupil; greater in the light → the large pupil.
- Look at the eyelids and eye movements. Mild ptosis with a small pupil suggests Horner syndrome; ptosis with a large pupil and limited eye movements suggests a third nerve palsy.
- Test the near response. A pupil that constricts better to a near target than to light shows light–near dissociation.
- Confirm with pharmacologic tests when the diagnosis is uncertain (see the table).
Horner vs Adie vs third nerve palsy vs Argyll Robertson
| Condition | Abnormal pupil | Key signs | Confirming test |
|---|---|---|---|
| Horner syndrome | Small; anisocoria greater in the dark | Mild ptosis, slightly raised lower lid, slow redilation in the dark (dilation lag), sometimes reduced sweating | Apraclonidine drops dilate the Horner pupil and reverse the anisocoria; cocaine drops fail to dilate it |
| Adie tonic pupil | Large; anisocoria greater in the light | Poor light reaction, slow sustained constriction to near and slow redilation, segmental iris sphincter palsy | Dilute pilocarpine (about 0.1%) constricts the affected pupil (denervation supersensitivity) |
| Third nerve palsy with pupil involvement | Large; anisocoria greater in the light | Ptosis, eye down and out, limited elevation, depression and adduction | Urgent vascular imaging (CT or MR angiography) to exclude an aneurysm |
| Argyll Robertson pupil | Both small and irregular | Bilateral light–near dissociation, poor dilation in the dark | Serology for syphilis |
| Pharmacologic mydriasis | Large; does not react | No ptosis and normal eye movements | Does not constrict even to 1% pilocarpine |
Horner syndrome in brief
Horner syndrome is interruption of the three-neuron sympathetic pathway to the eye: first order (hypothalamus to the upper thoracic spinal cord), second order (spinal cord over the lung apex to the superior cervical ganglion) and third order (along the internal carotid artery to the eye). The pupil is small but still reacts to light and near.
Second-order causes include apical lung tumors (Pancoast tumor) and neck or chest surgery; third-order causes include internal carotid artery dissection and cavernous sinus disease. A new, painful Horner syndrome, especially with neck pain or headache, must be treated as a possible carotid artery dissection until proven otherwise.
Adie tonic pupil in brief
Adie tonic pupil results from damage to the ciliary ganglion or short ciliary nerves, often after a viral illness, and typically affects young adults, more often women. The pupil is large, reacts poorly to light, but constricts slowly to sustained near effort and redilates slowly (light–near dissociation). Over years it may become smaller. With reduced deep tendon reflexes it is called Holmes–Adie syndrome. It is benign, and a classic presentation does not need neuroimaging.
Why the pupil matters in a third nerve palsy
Pupillomotor fibers run on the outer surface of the third nerve, where an expanding aneurysm (classically of the posterior communicating artery) compresses them early. A third nerve palsy with a dilated pupil is therefore an emergency until an aneurysm has been excluded. Microvascular palsies from diabetes or hypertension usually spare the pupil because the ischemia affects the core of the nerve — but pupil sparing alone does not remove the need for careful assessment and close follow-up.
Practice it on the virtual patient
- Open Horner syndrome in the right eye and compare the pupils and eyelids.
- Switch to Adie tonic pupil and test light, then the near target, to see light–near dissociation.
- Compare a complete third nerve palsy with a pupil-sparing third nerve palsy.
- Finish with the bilateral Argyll Robertson pupil.
Frequently asked questions
Which pupil is abnormal in anisocoria?
If the anisocoria is greater in dim light, the smaller pupil is abnormal because it fails to dilate. If it is greater in bright light, the larger pupil is abnormal because it fails to constrict.
What is physiological anisocoria?
Physiological (simple) anisocoria is a small difference in pupil size, usually 1 mm or less, seen in about one in five healthy people. It is about the same in light and dark, both pupils react normally, and there is no ptosis or eye movement problem.
What is light–near dissociation?
Light–near dissociation means the pupils constrict better to a near target than to light. Causes include Adie tonic pupil, Argyll Robertson pupil, dorsal midbrain (Parinaud) syndrome, severe bilateral optic nerve or retinal disease, and aberrant regeneration of the third nerve.
Does a Horner pupil react to light?
Yes. A Horner pupil constricts normally to light and near. The problem is weak sympathetic dilation, which is why the anisocoria is larger in the dark and the pupil redilates slowly.
Related guides
- RAPD and the swinging flashlight test Perform the swinging flashlight test, grade a Marcus Gunn pupil and know what causes it.
- Third, fourth and sixth cranial nerve palsies and the three-step test Recognize each ocular motor palsy, run the three-step test and spot the red flags.
- Internuclear ophthalmoplegia (INO), one-and-a-half syndrome and gaze palsies Localize INO, one-and-a-half syndrome, gaze palsies and Parinaud syndrome from eye movements.