Table 11.1 Features of an Adie’s pupil

Day 1: Large pupil size in darkness and in bright light Unresponsive to light stimulation and to near

effort

Sectoral palsy of the iris sphincter (seen under magnification)

Week 1: Cholinergic denervation supersensitivity to dilute pilocarpine

Week 8: Light-near dissociation

Slow, sustained (tonic) pupillary constriction during and after near effort

Month 6: Baseline pupil size in room light begins to decrease

weeks following denervation injury. The most commonly used pharmacologic agent for demonstrating such supersensitivity is dilute ( 18 %) pilocarpine. This solution can be made by drawing up 0.1 cc of 1% pilocarpine with 0.7 cc of sterile saline in a 1 cc tuberculin syringe. The proposed criterion for a positive response is either (1) the affected pupil constricts 0.5 mm more than the unaffected pupil or (2) the suspected pupil, which was larger than the normal pupil before instillation of pilocarpine, becomes the smaller pupil after instillation. Denervation supersensitivity can be demonstrated in about 80% of patients with an Adie’s pupil but takes several days to develop (Table 11.1). It is important to note that occasional patients with a dilated pupil from a third nerve palsy (i.e. preganglionic denervation) may also exhibit such supersensitivity. Therefore, the presence of cholinergic supersensitivity is not definitive evidence of an Adie’s pupil but must be taken into consideration with the other clinical findings.

In the reinnervation stage, the short ciliary nerves regenerate and reconnect to their end organs. The relative abundance of resprouting accommodative fibers leads to recovery of accommodation (near vision). In addition, accommodative fibers mistakenly make connections to the iris sphincter. This aberrant reinnervation leads to recovery of pupillary constriction when focusing at near but

with a slow and delayed (tonic) movement. Because the number of surviving pupilloconstrictor fibers is sparse, the pupillary light reflex remains poor or absent. This combination of a poor pupil light reflex with good near response is termed light-near dissociation.

Tonic pupils may occur from a variety of local processes affecting the ciliary ganglion, such as orbital trauma (accidental or iatrogenic), tumor, ischemia or infection. Tonic pupils may also occur as a manifestation of a more widespread autonomic process, such as diabetic or alcoholic peripheral neuropathy, and in these cases both pupils are affected. However, most cases of tonic pupil occur as a spontaneous unilateral condition, usually in women between the ages of 20 and 50 years and it is this idiopathic form that has been termed an Adie’s tonic pupil. When diminished muscle stretch reflexes are an associated finding, the condition is called Adie or Holmes–Adie syndrome. Neuro-imaging is not indicated for the patient with a typical Adie’s pupil.

Diagnosis: Adie’s tonic pupil

Tip: For practical purposes, isolated unilateral pupillary dilation in an alert and neurologically intact patient is not a sign of third nerve compression. Likely causes are Adie’s tonic pupil or pharmacologic mydriasis.

Acute unilateral visual loss with disc edema

Case: A 62-year-old farmer awoke with decreased vision in the left eye. Specifically, he described darkening of the bottom half of vision in that eye unassociated with head or eye pain, photopsias, other focal neurologic deficits or systemic symptoms. His medical history was positive for hypertension and hyperlipidemia. Three weeks earlier an additional anti-hypertensive medication had been added. Five days after onset, examination showed visual acuity of 20/25 OD and 20/40 OS with a 2+ left RAPD. Goldmann perimetry demonstrated an inferior altitudinal defect in the left eye and a full field in the right eye (Figure 11.1A). Fundus examination

showed swelling of the superior half of the left optic disc; the right disc was normal in appearance but “crowded”, with a small physiologic cup (Figure 11.1B).

Additional testing included an MRI of brain and orbits with contrast, a cranial MRA, carotid Dopplers, a transthoracic echocardiogram, visual evoked potential, and a variety of blood tests for

coagulopathy, all of which were normal or negative. One month later, disc edema had resolved leaving superior pallor, but his visual field defect was unchanged.

Can you diagnose the cause of this patient’s acute monocular visual loss based on the clinical findings? Are ancillary tests needed?

This patient presented with an acute, painless, unilateral optic neuropathy with altitudinal field loss and corresponding segmental disc edema. These clinical findings are sufficiently characteristic of non-arteritic anterior ischemic optic neuropathy (NAION) that little ancillary testing is needed. Specifically, cranial, carotid and cardiac imaging are not likely to add anything relevant to management decisions.

Discussion: NAION is a relatively common disorder, typically affecting middle-aged and older individuals. Visual loss is usually painless and often present upon awakening. An inferior altitudinal defect is the most common pattern of visual loss, frequently with preservation of normal visual acuity. Optic disc edema may be diffuse or segmental and peri-papillary splinter hemorrhages are common. Visual loss is most often maximal at onset, but up to one-third of patients experience further decline of vision over the next 10 days, termed progressive NAION. Once disc edema has resolved, usually within a few weeks, further visual loss is highly unlikely. Some modest improvement of visual acuity is common in the months following an episode of NAION but visual field defects are typically permanent. A repeat episode in the same eye is rare; however, 15 to 25% of patients will experience a similar attack in the fellow eye in the future.

The pathogenesis of NAION is multifactorial, including some degree of atherosclerosis and an underlying predisposing optic disc structure. Patients with NAION typically have a crowded optic disc with little or no physiologic cup, termed a “disc- at-risk”. In addition to these predisposing factors, recent interest has focused on the role of systemic

hypotension in the pathogenesis of this disorder. Occasionally episodes of profound hypotension (e.g. cardiac arrest) precipitate ischemic optic neuropathy. In addition, a possible role of less cataclysmic nocturnal hypotension, particularly that induced by anti-hypertensive medication taken in the evening, has been posited in the pathogenesis of this disorder. Other mechanisms that may contribute to optic nerve infarction in certain cases include vasospasm, loss of local autoregulation, and the metabolic and circulatory changes that occur in sleep apnea syndrome. Acquired and hereditary coagulopathies are not usually identified in patients with NAION, though such factors may play a role in occasional patients under age 50 years who lack the usual predisposing conditions.

Notably absent from the above list of etiologic factors are carotid artery disease and emboli. In contrast to vaso-occlusive events in the retinal circulation, NAION is rarely the result of embolic occlusion. Due to the branching pattern of the ocular circulation, emboli entering the ophthalmic artery are likely to proceed via laminar flow to the central or branch retinal arteries. In contrast, the posterior ciliary arteries emerge more at right angles from the ophthalmic artery and are therefore not susceptible to emboli. While rare cases of ischemic optic neuropathy secondary to complete carotid occlusion, carotid dissection or emboli have been reported, it is important to note that carotid artery disease has not been found in a higher percentage of patients with NAION as compared to age-matched controls. When carotid artery stenosis is found in a patient with NAION, it is just as likely to involve the contralateral side as the side with the visual loss. Specific features that suggest carotid artery disease may have played a role in an episode of NAION include preceding transient monocular visual loss, dimming of vision with changes of posture or exertion, ipsilateral pain and associated Horner syndrome, and in these settings carotid ultrasonography may be appropriate. In the large majority of patients with NAION, however, carotid artery imaging is not indicated. If carotid imaging is obtained in a patient with NAION and hemodynamically