Adie Pupil

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Article initiated by:

Alexander L. Ringeisen, MD, Andrew Go Lee, MD, Eric Lane Crowell, MD, MPH, Junru Yan, Nita Bhat, MBBS, MS, Shruthi Harish Bindiganavile, MBBS, MS, Kevin.Rolni

All contributors:

Andrew Go Lee, MD, Brad H. Feldman, M.D., Eric Lane Crowell, MD, MPH, Kevin Rolnick, Koushik Tripathy, MD (AIIMS), Nita Bhat, MBBS, MS, Shruthi Harish Bindiganavile, MBBS, MS, Nagham Al-Zubidi, MD, Alexander L. Ringeisen, MD, Nita Bhat, MBBS, MS

Assigned editor:

Nagham Al-Zubidi, MD

Review:

Assigned status Up to Date

 by Nagham Al-Zubidi, MD on April 4, 2024.

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Adie Pupil

DiseasesDB

29742

ICD-10

H57.0,H57.0,H57.0

MeSH

D000270

Adie Tonic Pupil

Disease Entity

Tonic Pupil ICD-10: H57.051 (right), H57.052 (left), H57.053 (bilateral)

Disease

Adie tonic pupil, known as Adie’s Syndrome or Holmes-Adie Syndrome, is a disorder in which there is parasympathetic denervation of the afflicted pupil resulting in a poor light but better and tonic near constriction. The affected pupil, either unilateral or bilateral typically initially appears abnormally dilated at rest and has poor or sluggish pupillary constriction in bright light. Constriction is typically more notable with the near reaction and typically remains tonically constricted with slow re-dilation with segmental paralysis of the iris sphincter. Patients may also present with decreased deep tendon reflexes in the full Holmes-Adie Syndrome. (Leavitt, 333) The entity is named after William John Adie, an Australian neurologist who extensively described the features. However, it may be noted that the tonic pupil was initially described in 1931 nearly synchronously by Adie, Morgan, Symonds, and Holmes in (2-4)

Epidemiology

Adie tonic pupil has a prevalence of 2 per 1000 population and occurs in a 2.6:1 female to male ratio with an average age of onset of 32 years (Thompson, 590). While 80 percent of Adie tonic pupils are unilateral, bilateral involvement typically has an incidence of 4 percent per year. (Thompson 618)

General Pathology

Damage to the parasympathetic ciliary ganglion may result in a tonic pupil. The parasympathetic fibers of the eye travel with the third cranial nerve to synapse at the ciliary ganglion before innervating the iris and the ciliary body. Typically, there are 30 times the number of axons supplying the ciliary body compared to those for the iris. After damage to the ciliary ganglion occurs, a process known as denervation supersensitivity occurs by which postsynaptic receptors are upregulated to facilitate reinnervation. However, the reinnervation process is often aberrant and fibers intended for the ciliary body may end up targeted to the pupil, a process known as aberrant regeneration (McGee, 171). As a result, patients develop Light-Near dissociation of the pupil by which the near accommodation produces more miosis compared to response to light, the reaction which is tonic. The tonic reaction is the result of the iris sphincter supersensitivity to acetylcholine. Roughly 80% of cases are unilateral but can become bilateral (4% chance per year). (Thompson, 618).

Causes

Most cases of the tonic pupil are idiopathic and referred to as the Adie tonic pupil. However, a tonic pupil can also be caused by viral infection, trauma, vasospasm due to migraine, ocular surgery, and tumors, among other potential causes. The ciliary ganglion can also be affected in other systemic autonomic or peripheral neuropathies to result in the tonic pupil such as Ross syndrome and Harlequin syndrome (Shin, 1841)

Diagnosis

Exam

Typical patients with Adie tonic pupil present with incidental finding of anisocoria. Initially, the tonic pupil appears larger than the unaffected eye. However, it is important to note that the affected pupil tends to become smaller over time in the chronic Adie tonic pupil. Slit lamp examination of the pupil often shows sectoral palsy of the iris sphincter, with vermiform movements of the pupillary margin (AAO, 4). To correctly form a diagnosis, it is important to examine the degree of anisocoria in the light and in the dark and to examine the pupillary reaction to light and to accommodation. Examination reveals anisocoria greater in the light compared to in the dark indicating dysfunction of the parasympathetically innervated iris sphincter muscle in the affected eye ( large pupil is abnormal). Upon initial exam, patients with Adie tonic pupil will demonstrate increased pupillary constriction to accommodation compared to light, also known as the light-near dissociation. However, this finding is not specific to Adie tonic pupil and can also be found in patients with bilateral anterior afferent visual pathway disease, Argyll Robertson pupil, diabetes, or dorsal midbrain lesions (UpToDate, Lee, 5). The affected pupil can be distinguished from these other causes by testing the tonicity of the constriction. In Adie tonic pupil, due to the acetylcholine sensitivity developed during the reinnervation process, typically has a strong and tonic pupillary response with a slow and sustained relaxation after constriction compared to the normal eye (AAO, 4)

Symptoms

Patients with Adie tonic pupil may present with symptoms relating to their sphincter dysfunction such as ranging from photophobia and difficulty to adapting to the dark. Ciliary muscle dysfunction may also present with symptoms of blurry vision both for near and far vision and during transitions and anisocoria. (Hope Ross et al, 608)

Diagnostic procedures

The denervated sphincter muscles can show increased sensitivity to diluted pilocarpine (0.125%) due to up regulation of receptors in about 80% of cases. Dilute pilocarpine (0.125 or 0.1 percent) can be made by diluting readily available commercial 1% solution with sterile saline. (Leavitt, 333) After 30-60 minutes the affected pupil will constrict more than the normal pupil. This test, however, is not specific for the Adie tonic pupil where there is postganglionic parasympathetic denervation. Supersensitivity has also been demonstrated in some preganglionic oculomotor nerve disorders (Leavitt, 333). Absent supersensitivity does not necessarily rule out diagnosis of Adie tonic pupil especially if it is in the acute setting as regeneration of nerves may not have yet occurred.

Differential diagnosis and additional tests

Adie tonic pupil is most commonly an idiopathic condition. It is important when faced with a picture of anisocoria, tonic pupil, or light-near dissociation to rule out other potentially more serious diagnoses: (McGee, 174):

1. Orbital trauma
2. Orbital tumor
3. Intracranial hemorrhage/stroke with third nerve palsy
4. Varicella-zoster infection (ophthalmic branch of trigeminal nerve)
5. Syphilis (Argyll Robertson pupil, generally bilateral, small, brisk redilation)
6. Miller Fisher syndrome
7. Charcot Marie Tooth disease
8. Systemic dysautonomia (Ross syndrome)
9. Diabetes
10. Chronic alcoholism
11. Multiple sclerosis
12. Herpes zoster
13. Neurosarcoidosis

When considering these additional potential diagnoses, it may be valuable to obtain syphilis serologies and check for history of diabetes, trauma, neurologic diseases

Management

Treatment and Prognosis

The Adie tonic pupil is a benign condition and generally patients only require reassurance. However, patients may experience photophobia and blurry vision. Accommodative paresis may resolve with time, ranging from months to years. However, patients may experience increased light-near dissociation over time since the pupil’s reaction to light does not typically recover (UpToDate, Lee, 5) While in general treatment is not required for Adie tonic pupil, dilute topical pilocarpine or physostigmine can be used for symptomatic relief in cases with severe photophobia. It must be noted that these medications can precipitate ciliary spasm, brow ache, worsen anisocoria, or induce nearsightedness (Thompson, 602). In patients with persistent accommodative paresis, frosted bifocal segments may be used to correct for vision. If an underlying systemic cause for the tonic pupil is suspected, patients should have treatment directed towards their systemic neuropathies.

Additional Resources

• Boyd K, DeAngelis KD. Anisocoria. American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/anisocoria-5. Accessed November 17, 2022.
• Porter D, DeAngelis KD. Adie's Pupil. American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/adies-pupil-list. Accessed November 17, 2022.