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Ophthalmic Pearls/Neuro-ophthalmology

Diagnosing Pupil Abnormalities

By Luz Maria Arieu, MD, and David A. Chesnutt, MD
Edited by Sharon Fekrat, MD, and Ingrid U. Scott, MD, MPH

When pupillary size differs, physiologic anisocoria is most often to blame. However, anisocoria must be systematically evaluated, as it may signal a history of trauma or the presence of a serious, potentially life-threatening condition, such as an aneurysm or a metastasis.

Exam Basics
Although anisocoria of 2 millimeters or less is often physiologic, an imbalance between the two divisions of the autonomic nervous system is the basis for pathologic anisocoria.

Regardless of whether the anisocoria is physiologic or pathologic, a complete eye examination is the best way to sort out the underlying cause of the difference in pupil size.

When examining a patient with anisocoria, the first step is to determine whether the smaller or the larger pupil is the abnormal one. A good rule of thumb is based on the comparison of the anisocoria in dim and bright illumination:

• If the anisocoria is more pronounced under dim illumination, the smaller pupil is usually the abnormal one, as the sympathetically innervated dilator muscle isn’t causing the normal dilation in the dark.
• Conversely, if the anisocoria is greater under bright illumination, the larger pupil is usually abnormal, because the parasympathetic input to the pupillary sphincter is deficient.

Abnormal Pupil Findings
Pharmacologic testing (see flowchart) can help pinpoint the diagnosis of the following clinically important pupil findings:

1. Physiologic anisocoria. Pupils tend to be round and regular in shape and to have a 1-mm difference. Anisocoria is considered essential (benign and central anisocoria) if the difference in pupil size is greater than 1 mm but pharmacologic testing reveals no defect. In physiologic anisocoria, both pupils react briskly to light and near stimuli. The difference in pupil size is maintained under normal room light and in the dark. In general, physiologic anisocoria is not associated with any disease.

2. Traumatic mydriasis. Iris injury may occur in patients with head and orbit trauma, if the iris sphincter is damaged. The pupil may be irregular, and its reaction to light and accommodation varies, depending on the extent of the damage. Anisocoria is more evident in bright light.

3. Pharmacologic mydriasis. Either inadvertent or intended exposure to mydriatics or certain plants can cause pharmacologic mydriasis. One or both pupils may be affected. They tend to be very dilated, large and round (7 to 8 mm), and their reaction to light and accommodation is absent. Anisocoria is more evident in bright light. There is no constriction in response to either pilocarpine 1 to 2 percent or to other miotics.

4. Oculomotor palsy. Pupil dilation may be the only sign of partial oculomotor palsy (third nerve palsy) in some clinical scenarios, such as basal meningitis. Usually, one pupil is affected; it is dilated, round and fixed at 5 to 6 mm. Anisocoria is more evident in bright light. The affected pupil dilates in response to mydriatics and constricts in response to miotics (including pilocarpine 1 to 2 percent).

5. Adie’s tonic pupil. A tonic pupil is seen with diseases of—or injury to—the ciliary ganglion. In 90 percent of cases, unilateral vermiform movements (sphincter palsies) are present. The affected pupil reacts poorly to light and better to near stimulus, although the reaction is slow and tonic. Anisocoria is more evident in bright light. Pupils dilate in response to mydriatics and constrict in response to miotics (including pilocarpine 0.125 percent) and to weak cholinergics such as methacholine (Mecholyl) 2.5 percent.

6. Sylvian aqueduct syndrome. A lesion in the midbrain is usually responsible. Both pupils are middilated and may be oval in shape; they react poorly to light, with a better reaction to a near stimulus. In addition, they dilate in response to mydriatics and constrict in response to miotics. Anisocoria is maintained despite changes in room lighting.

7. Argyll Robertson. This relatively rare condition is usually associated with tertiary syphilis that involves the midbrain. However, Argyll Robertson–like pupils also may be seen in diabetes, alcoholism, encephalitis and some degenerative disorders. Both pupils usually are small and irregular. They react poorly to light and better to near accommodation, and they dilate poorly in response to mydriatics and constrict in response to miotics. Anisocoria is maintained despite changes in room lighting.

8. Horner’s syndrome. A lesion at any point along the sympathetic pathway results in Horner’s syndrome. The lesion may be due to vascular occlusion, tumors, surgery or trauma. The affected pupil is small and round, but both pupils react briskly to light and accommodation. Anisocoria is more evident in the dark. The affected pupil dilates poorly in response to cocaine 4 to 10 percent. In cases of postganglionic Horner’s syndrome, the pupils do not dilate in response to hydroxyamphetamine (Paredrine) 1 percent; however, pupils dilate normally with hydroxyamphetamine in cases of central or preganglionic Horner’s syndrome.

Dr. Arieu is a research fellow and Dr. Chesnutt is a neuro-ophthalmologist; both are at Duke University Medical Center in Durham, N.C.

Part one of this two-part article ran in the March 2002 issue of EyeNet.

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