Last updated:
9/25/2025
Years published: 1991, 1999, 2007, 2016, 2019, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Helmut Wilhelm, Prof. Dr. med, Centre for Ophthalmology, University Eye Hospital, University of Tübingen, Tübingen, Germany, for assistance in the preparation of this report.
Adie syndrome, or Holmes-Adie syndrome, is a rare neurological disorder affecting the pupil of the eye. In most people with this syndrome, the pupil is larger than normal (dilated) and slow to react in response to direct light. Absent or poor tendon reflexes are also associated with this disorder. In most cases, the cause is unknown (idiopathic), but Adie syndrome can occur due to other conditions such as trauma, surgery, lack of blood flow (ischemia) or infection. In rare cases localized disturbance of sweat secretion is associated with Adie syndrome (Ross syndrome).
Adie syndrome is usually nonprogressive and limited to damage to the autonomic nervous system, which is the portion of the nervous system that controls or regulates certain involuntary body functions including the reaction of the pupils to stimuli.
The term Adie syndrome is used when abnormalities of the pupil and loss of deep tendon reflexes are present. However, these findings may not develop at the same time. When only abnormalities affecting the pupil are present, the disorder may be referred to as Adie’s pupil, Adie’s tonic pupil or, most commonly, tonic pupil. When a person’s pupils are of unequal size, the term anisocoria may be used.
Normally, the pupil gets smaller (constricts) in bright light or when focusing on nearby objects. It opens wider (dilates) in dim light or darkness, when focusing on distant objects, or when a person is excited.
In people with Adie syndrome, the affected pupil is usually larger than normal (dilated) most of the time and shows little or no constriction in response to direct light. It is often slightly oval rather than perfectly round. The pupil does tighten, but slowly, when focusing on close objects, a normal focusing reflex called accommodation or the near response (the eye adjusts its focus for near work). Because this focus can be weak at first, some people notice difficulty reading or seeing objects that are near clearly. This temporary weakness in the eye’s focusing ability is called “accommodative paresis”.
When the pupil is examined under magnification (with a loupe or microscope), a typical pattern may be seen at rest or during near focus where some segments of the iris sphincter muscle constrict while others do not. This has been described as a movement resembling an earthworm.
Over months or years, the pupil that was initially larger than the other eye may become smaller than the unaffected pupil. After stopping focusing on a near object, the affected pupil may remain small or re‑dilate very slowly, sometimes taking several minutes to return to its usual (dilated) size.
Some people have no noticeable symptoms from the affected pupil. Others may have blurry vision or sensitivity to bright light (photophobia). Adie syndrome usually affects one eye, although the other eye may become involved over time. The disorder does not typically cause severe disability.
There are also reports in the medical literature that some people with Adie syndrome may have other problems involving the autonomic nervous system (the body’s automatic control system) such as issues affecting cardiovascular function (for example, heart rate or blood pressure regulation).
Other symptoms may include:
Headache, facial pain, or emotional fluctuations may occur in some affected people.
The exact cause of Adie syndrome is usually unknown (idiopathic). It is thought that most cases result from inflammation or damage to the ciliary ganglion, a cluster of nerve cells found in the eye socket (orbit) just behind the eyes, or damage to the post-ganglionic nerves. The ciliary ganglion is part of the parasympathetic nervous system, which is itself part of the autonomic nervous system. The parasympathetic nervous system relaxes the body and inhibits or slows down high energy functions.
The ciliary ganglion supplies nerves (innervates) to the eyes. These nerves carry signals that help to control the pupil’s response to stimuli such as growing smaller or larger in response to light, dark or other stimuli. These nerves communicate with the iris sphincter muscle, the muscle that controls how much light enters the pupil (causing the pupil to either contract or grow larger). However, most of the cells of the ciliary ganglion (97%) help the eyes change focus from far to near objects (accommodation) and supply the ciliary muscle which adjusts the crystalline lens of the eye to near vision.
In Adie syndrome, both these nerve cells are damaged. Because there are so many nerve cells that help with accommodation, usually enough survive. Therefore, accommodation difficulties are not obvious or are less obvious. Eventually, the damaged nerves may regenerate, but some do so improperly (aberrant regeneration). Because the nerve cells serving the pupillary sphincter are very few it is unlikely that many of them regenerate and restore the pupillary light reflex. However, cells that supply the ciliary muscle may also suffer aberrant regeneration and regenerate and innervate not only the ciliary muscle but also the pupillary sphincter muscle. This explains why the near response in a tonic pupil is present but slow. It is being elicited by nerve cells that were designed for accommodation, a slower movement than pupillary constriction. In most people, damage to the ciliary ganglion or the postganglionic nerves is thought to be caused by a viral infection.
There is also evidence that autoimmune processes may play a role. Tumor, trauma and inflammation (especially syphilis) have also been linked to Adie syndrome. The syndrome has also occurred as a complication of surgery to the area of the eye socket. It is also seen in giant cell arteritis, a severe vasculitis of the elderly. There are rare cases where a tonic pupil has occurred as a paraneoplastic disorder, but so far only in people where the malignant disease already was known.
The loss of deep tendon reflexes is thought to be caused by damage to the dorsal root ganglions, a cluster of nerve cells in the root of spinal nerves.
The prevalence of Adie’s pupil (not the full syndrome) is approximately 2 per 1,000 in the general population. The exact incidence or prevalence of Adie syndrome itself is unknown. Adie syndrome affects females more often than males by a ratio by some estimates of 2.6:1 for cases where the cause is unknown. Young adults, usually between the ages of 25 to 45, are most affected.
A diagnosis of Adie syndrome can be made by a thorough clinical evaluation and a detailed patient history. A complete eye examination by an ophthalmologist is recommended. An eye doctor may use water-downed (diluted) pilocarpine to test the pupil’s reaction. Pilocarpine, given in the form of eye drops, is a drug that causes the pupils to grow smaller (constrict). In individuals with Adie syndrome, the affected pupil, which does not constrict in response to light, will constrict in response to dilute pilocarpine (0.05 – 0.1%) to which a normal pupil would not constrict. If the pupil dilation is caused by contact with scopolamine or atropine, the pupil will not constrict even to higher concentrations (0.5 – 1%) which cause normal pupils to constrict vigorously.
In some people with tonic pupils’ constriction is observed when the conjunctiva is touched or irritated e.g. when grating onions. An eye doctor may also compare the size of the affected eye versus the unaffected eye in darkness and light as well as evaluating the response of the pupil when focusing on an object that is close.
An eye doctor may use a slit-lamp, a device that allows them to examine the eyes under high magnification, to detect segmental paralysis and a flattened border of the pupil so that the pupil appears irregularly shaped. In some people, worm-like (vermiform) movements of the iris can be seen under slit-lamp examination. In most people, the pupil seems slightly distorted to an oval shape.
Most people with Adie syndrome do not need treatment. Once the condition is properly diagnosed and explained, reassurance is often all that is needed, as the disorder is benign and does not usually lead to serious complications.
If the tonic pupil is caused by another underlying health issue, such as an autoimmune disorder, nerve damage, or infection, treatment focuses on managing that condition.
In many people, the problem improves naturally over several months without the need for treatment. However, if the focusing problem persists, special reading glasses may be helpful. These may include bifocal lenses with different strengths for each eye, or a frosted lens segment on one side to reduce eye strain and double vision.
For people who experience sensitivity to light or difficulty seeing clearly due to the uneven pupil size (anisocoria), low-dose medicated eye drops such as pilocarpine or physostigmine may offer some relief. These drops help make the large pupil smaller, improving vision and reducing glare. However, they can sometimes cause side effects such as eye strain, headache, or blurred vision. They may also make the difference in pupil size more noticeable, which some people may find cosmetically bothersome.
Most people with Adie syndrome can live normal, healthy lives without serious effects. The initial problem with focusing up close (accommodative paresis) often improves on its own. However, the pupil usually does not regain its normal reaction to light, and the difference between how the pupil reacts to light versus how it focuses on near objects may become more noticeable over time. This is known as light–near dissociation.
In some people, the affected pupil, which starts out larger than normal, may gradually become smaller over the years. This is sometimes referred to as a “little old Adie” pupil.
In rare cases, Adie syndrome has been linked to a type of eye pressure problem called angle-closure glaucoma, especially in people who have a specific eye structure known as plateau iris configuration. Although this is very uncommon, regular follow-ups with an eye specialist are recommended to monitor eye health and prevent complications.
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TEXTBOOKS
Rosenfield M, Logan N. Eds. Tonic or Adie’s Pupil. In: Optometry: Science, Techniques and Clinical Management. 2nd ed. Butterworth Heinemann Elsevier, St. Louis, MO; 2009:145.
Bartlett JD, Jaanus SD. Eds. Adie’s Syndrome. In: Clinical Ocular Pharmacology. 5th ed. Butterworth Heinemann Elsevier, St. Louis, MO; 2008:357-360.
JOURNAL ARTICLES
Siddiqui AA, Clarke JC, Grzybowski A. William John Adie: the man behind the syndrome. Clin Experiment Ophthalmol. 2014;42:778-784. https://onlinelibrary.wiley.com/doi/10.1111/ceo.12301/epdf
Szabo B, Popescu LA, Rusu A. Tonic pupil, pupil Adie syndrome Adie Holmes: current reassessment of terminology – a clinical case. Oftalmologia. 2012;56:46-51. https://www.ncbi.nlm.nih.gov/pubmed/23713338
Wakerley BR, Tan MH, Turner MR. Teaching video neuroimages: acute Adie syndrome. Neurology. 2012;79:e97. https://www.ncbi.nlm.nih.gov/pubmed/22965679
Guaraldi P, Mathias CJ. Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome. J Neurol Neurosurg Pyschiartry. 2011;82:1046-1049. https://www.ncbi.nlm.nih.gov/pubmed/20562402
Wilhelm H. Disorders of the pupil. Handb Clin Neurol. 2011;102:427-466. https://www.ncbi.nlm.nih.gov/pubmed/21601076
Bremner FD, Smith SE. Bilateral tonic pupils: Holmes-Adie syndrome or generalized neuropathy? Br J Ophthalmol. 2007;92:1620-1623. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095539/
Nolano M, Provitera V, Perretti A, et al. Ross syndrome: a rare or a misknown disorder of thermoregulation? A skin innervation study on 12 subjects. Brain. 2006;129:2119-2131. https://www.ncbi.nlm.nih.gov/pubmed/16837483
Triggs WJ, Brown RH Jr., Menkes DL. Case records of the Massachusetts General Hospital. Case 18-2006. A 57-year-old woman with numbness and weakness of the feet and legs. N Engl J Med. 2006;354:2584-2592. https://www.ncbi.nlm.nih.gov/pubmed/16775239
Martinelli P, Minardi C. Tonic pupil and tendon areflexia: the Holmes-Adie’s syndrome. Recenti Prog Med. 2001;92:605-608. https://www.ncbi.nlm.nih.gov/pubmed/11695306
Martinelli P, Minardi C, Ciucci G, et al. Neurophysiological evaluation of areflexia in Holmes-Adie syndrome. Neurophysiol Clin. 1999;29(3):255-62. https://www.ncbi.nlm.nih.gov/pubmed/10431290
Jacobson DM, Vierkant RA. Comparison of cholinergic supersensitivity in third nerve palsy and Adie’s syndrome. J Neuroophthalmol. 1998;18(3):171-75. https://www.ncbi.nlm.nih.gov/pubmed/9736199
Jacobson DM, Hiner BC. Asymptomatic autonomic and sweat dysfunction in patients with Adie’s syndrome. J Neuroophthalmol. 1998;18(2):143-47. https://www.ncbi.nlm.nih.gov/pubmed/9621272
INTERNET
Lee AG. Tonic Pupil. UpToDate. October 29, 2024. Available at: https://www.uptodate.com/contents/tonic-pupil Accessed Sept 22, 2025.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: Johns Hopkins University. Adie Pupil. Entry No:103100. Last Update: 1/29/2020. Available at: https://omim.org/entry/103100 Accessed September 22, 2025.
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