The first step in the analysis of pupillary asymmetry is to determine which of the pupils is abnormal. An abnormal larger pupil can be identified by a reduced direct and consensual light reaction. If the smaller pupil is causing asymmetry, it will fail to enlarge in response to shading both eyes, or reducing ambient light. More simply stated, light exaggerates the anisocoria caused by a third-nerve lesion, and darkness accentuates the anisocoria in the case of a Horner syndrome.
A persistently small pupil always raises the question of a Horner syndrome, a diagnosis that may be difficult if the ptosis is slight. In darkness, the Horner pupil dilates more slowly and to a lesser degree than the normal one because it lacks the pull of the dilator muscle (dilation lag). The diagnosis in the past had been confirmed by placing 1 or 2 drops of 2 to 10 percent cocaine in each eye; the Horner pupil dilates not at all or much less than the normal one. A more recently introduced approach that is more dependable and obviates the difficulties in obtaining cocaine is to apply the α-agonist apraclonidine to both eyes and observe the reversal of miosis on the affected side of Horner syndrome (the opposite effect to cocaine). Such responses to either drug will occur with a lesion at any point along the sympathetic pathway because lesions of the firstor second-order sympathetic neurons reduce the release of norepinephrine from third-order neurons. The reduction of neurotransmitter at the nerve endings in the ciliary dilator muscle greatly reduces the reuptake blocking effects of cocaine. If the subsequent (24 h after cocaine) application of the adrenergic mydriatic hydroxyamphetamine (1 percent) has no effect, the lesion can be localized to the postganglionic portion of the pathway as this drug releases any norepinephrine that may remain in the third-order neuron. Localization of the lesion to the central or preganglionic parts of the sympathetic pathway depends upon the associated symptoms and signs (see Chap. 26).
A variety of lesions, some of them purely ocular, such as uveitis, may also give rise to a dilated pupil.
Drug-induced iridoplegia is another cause of anisocoria. Not infrequently, particularly among nurses and pharmacists, a mydriatic fixed pupil is the result of accidental or deliberate application of an atropinic or sympathomimetic drug. We have observed this in house officers after they had participated in resuscitation from a cardiac arrest and been inadvertently sprayed with a sympathomimetic drug. Failure of 1 percent pilocarpine drops to contract the pupil provides proof that the iris sphincter has been blocked by atropine or some other anticholinergic agent. This is particularly the case when only one eye is affected.
As a rule, bilateral smallness of pupils does not pose a difficult diagnostic problem. The clinical associations, acute and chronic, have already been discussed. Long-standing bilateral Adie pupils tend to be small and show tonic near responses. They can be readily distinguished from Argyll Robertson pupils, which constrict quickly to near (accommodation) and redilate quickly on release from the near stimulus.
Figure 13-11 is a useful schematic, devised by Thompson and Pilley, for sorting out the various types of anisocoria.
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