Blunt trauma to the eye can cause miosis or mydriasis. The pupil may be relatively miotic after injury due to spasm, thereafter becoming midsized or mydriatic, with poor responses to light and near stimulation. Notches in the pupillary margin or transillumination defects near the sphincter muscle are evidence of sphincter damage. Mydriasis resulting from direct iris sphincter damage does not respond to topical pilocarpine (1% or 2%) and thus mimics pharmacologic mydriasis. Slit-lamp examination should help the clinician differentiate traumatic mydriasis from other types of mydriasis. When iris injury occurs in patients with head trauma, the dilated pupil may be mistakenly identified as a sign of CN III palsy due to uncal herniation.
Prolonged or recurrent angle closure can also impair pupillary function, as can intraocular surgery (Urrets-Zavalia syndrome).
When anticholinergic medications are accidentally or intentionally instilled in the eye, the pupil becomes dilated, and its reactivity to light and near stimulation is lost and accommodation is impaired. Drug-induced dilation causes paralysis of the entire sphincter, in contrast to a tonic pupil, which causes segmental sphincter paralysis. Slit-lamp examination can help the clinician make this distinction. When mydriasis is induced by an anticholinergic drug such as atropine, instillation of full-strength pilocarpine (1% or more) will not reverse the mydriasis. Mydriasis caused by neurologic disease such as Adie tonic pupil or CN III palsy is easily overcome with instillation of full-strength or even dilute pilocarpine. Pharmacologic mydriasis from topical dilating drops usually results in a large pupil, measuring greater than 7 mm. With adrenergic mydriasis, the pupil is large, the palpebral fissure is widened, and the conjunctiva may be blanched. Accommodation is not impaired. Pilocarpine 1% will cause some pupil contraction to an iris that has been dilated with α1-adrenergic agonists, but it won’t be as much as in an eye without adrenergic mydriasis.
Adie tonic pupil
Damage to the ciliary ganglion or short ciliary nerves (postganglionic parasympathetic nerve injury) produces an Adie tonic pupil, which is characterized by a large pupil with poor reaction to light but a strong and tonic pupillary response to near vision (light–near dissociation). The pupil experiences a slow tonic redilation on looking from near to far distances. Other characteristics include sectoral palsy of the iris sphincter (Fig 10-5), accommodative paresis, and denervation cholinergic supersensitivity.
During the acute denervation phase of a tonic pupil, the pupil is dilated and poorly reactive to light stimulation and accommodative effort. Slit-lamp examination of the iris using high magnification can help the clinician distinguish functional sphincter segments from nonfunctional sphincter segments. Iris crypts stream toward areas of normal sphincter function, and the stroma bunches up along the pupillary border in such areas, producing vermiform movements. Stromal thinning—even atrophy—is observed in areas of sphincter paralysis (see Fig 10-5).
Figure 10-5 Sectoral palsy of the iris sphincter in Adie tonic pupil. The pupil is not round. The sphincter contraction is strongest along its superior sector, seen as a puckering or “bunching up” of the iris stroma. The sphincter is paralyzed between the 7-o’clock and 9-o’clock sectors (arrows); the adjacent area of iris stroma appears thinned out and flattened.
(Courtesy of Rod Foroozan, MD.)
As the damaged short ciliary nerves regenerate, misguided accommodative fibers sprout onto the iris sphincter, and the pupil recovers its ability to constrict in response to accommodative (or near) effort. However, pupillary movement (both constriction in response to an accommodative stimulus and subsequent redilation) is delayed and slow, that is, tonic (Fig 10-6). This effect may account for patient reports of difficulty refocusing when switching from near vision to distance. The pupillary light reflex typically remains severely impaired.
Idiopathic tonic pupil is known as Adie tonic pupil. Approximately 70% of patients are female. Tonic pupils are unilateral in 80% of cases, but the second pupil may become involved later (4% of unilateral cases per year). Holmes-Adie syndrome includes other features, notably, diminished deep tendon reflexes and orthostatic hypotension.
Pharmacologic testing can be used to confirm the diagnosis of Adie tonic pupil. The denervated iris sphincter is supersensitive to weak parasympathomimetic solutions, such as dilute pilocarpine eyedrops (0.1%). This pilocarpine strength can be obtained by diluting commercial 1% solution with balance salt solution, artificial tears, or sterile saline. Sixty minutes after eyedrop application, the pupils are reexamined. If parasympathetic denervation is present, the affected pupil will have constricted more than the normal pupil (Fig 10-7). About 80% of patients with a tonic pupil demonstrate cholinergic supersensitivity, which develops within 5–7 days of denervation.
Figure 10-6 Left Adie tonic pupil. A, The left pupil reacts poorly to direct light stimulus, whereas the right pupil demonstrates a strong consensual response. B, Both pupils constrict as the patient fixates on a near target. The response of the left pupil to near effort is better than its response to light (light–near dissociation). C, After the patient refixates on a distant target, the right pupil quickly redilates. The left pupil is slow to redilate (it is smaller than the right pupil), a sign of tonicity.
(Courtesy of Lanning B. Kline, MD.)
Figure 10-7 Right Adie tonic pupil and its response to pharmacologic testing A, Right Adie tonic pupil at baseline in ambient room lighting. B, After instillation of pilocarpine (0.1%), the right pupil becomes miotic, demonstrating supersensitivity.
(Courtesy of Lanning B. Kline, MD.)
Patients with tonic pupils may have accommodative symptoms or photophobia but just as often are asymptomatic. Accommodative symptoms are difficult to treat but usually resolve spontaneously within a few months after onset. When photophobia is a problem, topical dilute pilocarpine (0.1%) may be helpful. With time (months to years), an Adie tonic pupil decreases in size but remains poorly reactive to light, resulting in anisocoria that is greater in the dark than in the light. Histologic examination of the ciliary ganglion in patients with Adie tonic pupil has shown a reduction in the number of ganglion cells.
A tonic pupil can be caused by local ocular or orbital processes such as surgery, trauma, laser procedure, infection (eg, herpes zoster virus, herpes simplex virus, syphilis, botulism), inflammation, or ischemia. Tonic pupils can also be a manifestation of widespread autonomic dysfunction consequent to diabetes mellitus, chronic alcoholism, dysautonomias, neurosyphilis, amyloidosis, sarcoidosis, the Miller Fisher variant of Guillain-Barré syndrome, or Charcot-Marie-Tooth disease. In addition to bilateral tonic pupils with mydriasis, botulism toxicity may also produce bilateral ptosis and ocular motility dysfunction.
Third cranial nerve palsy
Pupillary involvement in CN III palsy is almost always accompanied by ptosis and limited ocular motility (see Chapter 7). At times, the motility disturbance is subtle, requiring quantitation with prism and alternate cover testing. Pupillary dysfunction is an important factor in the evaluation of acute CN III palsy. When the pupil is involved, an aneurysm must be excluded (see Chapter 2, Fig 2-11). If the pupil is spared and all other functions of CN III are completely paretic, an aneurysm is unlikely, and microvascular ischemic disease is more probable.
Aberrant regeneration of CN III may cause mydriasis and a synkinetic pupillary reaction. (See images available at the NOVEL [Neuro-Ophthalmology Virtual Education Library] website at http://novel.utah.edu.) Portions of the pupillary sphincter contract with attempted movement of the eye, especially medially.
Czarnecki JS, Thompson HS. The iris sphincter in aberrant regeneration of the third nerve. Arch Ophthalmol. 1978;96(9):1606–1610.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.