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We would like to hear your feedback as we continue to refine this new version of the GARD website.
Home Browse by Disease Adie Syndrome Adie Syndrome
Adie syndrome is is a neurological disorder affecting the pupil of the eye and the autonomic nervous system. It is characterized by one eye with a pupil that is larger than normal that constricts slowly in bright light (tonic pupil), along with the absence of deep tendon reflexes, usually in the Achilles tendon. In most cases, the cause of Adie syndrome is unknown. Some cases may result from trauma, surgery, lack of blood flow, or infection. The term Adie syndrome is used when both the pupil and deep tendon reflexes are affected. When only the pupil is affected, the disorder may be referred to as Adie's pupil.
In the U.S., this disease is estimated to be less than
Population Estimate Symptoms Onset Symptoms * Cause * Specialists Genetic Testing * FDA Approved Drugs * Patient Organizations Resources
*Data may be currently unavailable to GARD at this time.
The most common ages for symptoms of a disease to begin is called age of onset. Age of onset can vary for different diseases and may be used by a doctor to determine the diagnosis. For some diseases, symptoms may begin in a single age range or several age ranges. For other diseases, symptoms may begin any time during a person's life.
The common ages for symptoms to begin in this disease are shown above by the colored icon(s).
This information comes from Orphanet
This section is currently in development. We recommend speaking with a doctor to learn more about this disease. 
Good communication between the patient, family, and medical team can lead to an accurate diagnosis. In addition, health care decisions can be made together which improves the patient’s well-being and quality of life.
The National Library of Medicine's Unified Medical Language System (UMLS) is used to classify and organize diseases and disease categories.
Reference: UMLS Vocabulary Standards and Mappings Downloads
Data from Orphanet and Human Phenotype Ontology (HPO) are used to provide information on a disease's symptoms, genes, inheritance, population estimates, and more.

Reference: Access aggregated data from Orphanet at Orphadata . Orphanet is an online database of rare diseases and orphan drugs. Copyright, INSERM 1997. Reference: Download data from HPO . Kohler S, Gargano M, Matentzoglu N, et al., The Human Phenotype Ontology in 2021 , Nucleic Acids Research, Volume 49, Issue D1, 8 January 2021, Pages D1207–D1217. 
Data from the National Center for Biotechnology Information's MedGen is used to provide genetic testing information available for a disease.

Reference: MedGen Data Downloads and FTP
Data from the National Library of Medicine's Newborn Screening Coding and Terminology Guide is used to note if a disease is included on Federal or State recommendations for newborn screening testing.

Reference: Data from the Newborn Screening Coding and Terminology Guide is available here. Downs SM, van Dyck PC, Rinaldo P, et al. Improving newborn screening laboratory test ordering and result reporting using health information exchange . J Am Med Inform Assoc. 2010 Jan-Feb;17(1):13-8. 
Content References: National Academies of Sciences, Engineering, and Medicine. 2015. Improving Diagnosis in Health Care . Washington, DC: The National Academies Press. U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion. (2015). Health Literacy Online: A Guide for Simplifying the User Experience .
GARD Genetic and Rare Diseases Information Center
Many rare diseases have limited information. Currently GARD is able to provide the following information for this disease:
This section is currently in development. 
Describe details about the symptoms. Because there may be many different causes for a single symptom, it is best not to make a conclusion about the diagnosis. The detailed descriptions help the medical provider determine the correct diagnosis. To help describe a symptom:

Working with a medical team to find a diagnosis can be a long process that will require more than one appointment. Make better health decisions by being prepared for the first visit with each member of the medical team.

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Nous vous accompagnons dans votre activité
Je trouve les évènements à proximité
Ils ont lancé leur entreprise avec l'Adie
À l'Adie, nous défendons l'idée que chacun peut devenir entrepreneur.
Inscrivez-vous à la prochaine réunion d'information de l'Adie près de chez vous !
Des ateliers gratuits pour créer son entreprise du 3 au 7 octobre
Séphora a créé son salon de beauté de chez elle, en région parisienne
« Je n’avais aucun apport et au début, je ne savais même pas ce qu’était un business plan. L’accompagnement de l’Adie a changé ma vie et celle de mes filles. »
Orlana, traiteure et animatrice culinaire itinérante sur son « Veloo »
« Malgré les incertitudes, j'ai toujours eu envie d’aller jusqu’au bout car je porte ce projet en moi depuis des années. J’accepte les aléas et suis prête à me réinventer s’il le faut, en composant de nouvelles recettes sur le piano de cuisine de mon triporteur. »
Jonathan a ouvert sa brasserie « Les Dalons » à Sainte-Marie, La Réunion
« Nous avons commencé notre activité de production et de vente en pleine crise des gilets jaunes. Aujourd’hui, nous continuons à nous développer dans un contexte de crise sanitaire. Nous nous adaptons en nous reposant sur nos savoir-faire et sur la confiance de nos clients. »
Franck fabrique des savons à froid, en respectant la nature et en alliant tradition et modernité
« Sauvons notre peau et la planète avec un bon savon bio, doux, hydratant et écologique ! »
« Lancer mon entreprise était un grand pas pour moi, un vrai risque. Je n’aurais jamais imaginé que tout irait aussi vite. »
Boris, poissonnier sur les marchés en Corrèze
« J'étais sûr de ne plus vouloir travailler pour un patron car il n’aurait plus rien à m’apprendre. »
Cécile, artisan designer textile à Guichen
« Je suis ravie d’avoir osé créer mon activité à mon idée et selon mes valeurs il y a maintenant un peu plus de deux ans. Il s’agit d’une entreprise à taille humaine avec de belles perspectives qui me permet de travailler à mon rythme et de proposer une vision alternative en termes de design textile, la mienne ! »
Bruno, rôtisseur à Brive-la-Gaillarde
« Entreprendre c’est courageux ! Il ne faut pas avoir peur de se lancer même s’il y a des moments compliqués. »
Odette, fabrication et vente de spécialités africaines sur les marchés
« Il n’y a pas beaucoup de risques à se lancer, si on échoue, il suffit de recommencer. »
Lyly, organisatrice de Food Mood Tour
« Mon message pour de futurs entrepreneurs : si vous avez envie de créer, foncez ! Parfois ce sera compliqué, mais vous allez gérer ! »
Benjamin, éleveur de lama dans le Var
Le contact de ces animaux auprès des publics sensibles, comme les maisons d’enfants, les personnes handicapées, ou en maison de retraites, en plus de leur redonner confiance, améliorent durablement leur quotidien.
« J’ai toujours voulu me mettre à mon compte. »
Grégory et Murielle font découvrir le kombucha à leurs clients
« Notre conseil à de futurs entrepreneurs : prendre le temps pour faire les choses, et rester raisonnable dans l’investissement du départ. »
Audrey, site de e-commerce Beachwear à La Réunion
 « La persévérance paie, il ne faut rien lâcher et les résultats sont là. Il est préférable de commencer maintenant, si ça ne fonctionne pas, je recommencerai ! » 
Louise, gérante d’un dépôt-vente à Riom
Louise, passionnée de vêtements de seconde main, reprend le dépôt-vente de sa ville.

René, concepteur de palettes recyclées
« En plus de mon associé et moi, j’emploie 8 salariés. Si je le pouvais, j’en aurais 15, mais pour le moment je ne peux pas financer le rythme de ce développement. Je suis même obligé de refuser des clients. »


↑ Jump up to: 1.0 1.1 1.2 1 Leavitt JA, Wayman LL, Hodge DO, Brubaker RF. Pupillary Response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil. American Journal of Ophthalmology. March 2002. 133:333-336.

↑ 2 Adie WJ. Pseudo-Argyll Robertson Pupils With Absent Tendon Reflexes: A Benign Disorder Simulating Tabes Dorsalis. Br Med J 1931; 1:928.

↑ 3 Morgan OG, Symonds CP. Internal Ophthalmoplegia with Absent Tendon-jerks. Proc R Soc Med 1931; 24:867.

↑ 4 Holmes G. Partial iridoplegia with symptoms of other diseases of the nervous system. Trans Ophthalmol Soc UK 1931; 51:209.

↑ Jump up to: 5.0 5.1 5.2 5.3 5 Thompson HS. Adie’s syndrome: some new observations. Trans Am Ophthalmol Soc 1977; 75:587.

↑ Jump up to: 6.0 6.1 6 McGee S. The Pupils. In: Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, PA: Elsevier; 2012:161-180.

↑ 7 Shin RK, Galetta SL, Ting TY, Armstron K, Bird SJ. Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin. Neurology. December 200. 55:1841-1846.

↑ Jump up to: 8.0 8.1 8 AAO. Pupil Efferent Defects. Anisocoria: Pupil Efferent Defects. https://www.aao.org/focalpointssnippetdetail.aspx?id=db4df9ab-f6ac-4331-91dd-9dec5fc34c47 . Accessed October 9, 2019.

↑ 9 Hope-Ross M, Buchanan TAS, Archer DB, Allen JA. Autonomic function in Holmes Adie Syndrome. Eye. 1990;4(4):607-612. doi:10.1038/eye.1990.85.


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

Adie tonic pupil, also 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) [1]
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) [2]
[3]
[4]

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). [5] While 80 percent of Adie tonic pupils are unilateral, bilateral involvement typically has an incidence of 4 percent per year. (Thompson 618) [5]

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). [6] 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). [5]

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) [7]

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). [8]
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) [8]

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) [9]

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) [1] 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). [1] 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.

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) [6] :


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

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). [5] 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.


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