Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 13 peer-reviewed journal articles Updated
Neurology

Symptoms & Differentiating Conditions

At a Glance

Holmes-Adie Syndrome is a benign condition marked by unequal pupil size, a sluggish pupil reaction to bright light, and a loss of deep tendon reflexes. These reflex changes are harmless and do not affect voluntary activities like walking or driving.

Understanding the symptoms of Holmes-Adie Syndrome (HAS) is the first step in distinguishing this benign condition from other, more urgent neurological issues. While the visual changes can be frustrating, HAS follows a specific pattern that helps doctors identify it [1][2].

Key Symptoms of Holmes-Adie Syndrome

The symptoms of HAS typically center on how the eye reacts to light and how the body’s nerves signal the muscles.

  • Unequal Pupil Size (Anisocoria): You may notice that one pupil is significantly larger than the other, especially in bright light [1][3].
  • Sluggish Light Reaction: The affected pupil may not constrict (shrink) at all when light is shown into it, or it may do so very slowly and “tonically,” meaning it takes a long time to return to its original size [4][5].
  • Light-Near Dissociation: This is a hallmark of the condition. While the pupil fails to react to light, it will constrict when you focus on something close up, such as a book or a phone [5][2].
  • Focusing Issues and Light Sensitivity: You may experience photophobia (discomfort in bright light) because the pupil stays wide open [5][6]. Additionally, you might have trouble shifting your focus from distant to near objects, causing blurred vision [5].
  • Diminished Reflexes (Areflexia): Many people with HAS lose their deep tendon reflexes, such as the knee-jerk or ankle-jerk reflex [1][7]. While this sounds alarming, it does not affect your daily life. The reflex (the involuntary jerk when a doctor taps your knee) is gone, but this does not impact your voluntary muscle control. You will not notice it when walking, driving, playing sports, or catching your balance if you trip [2].

What It Is NOT: Differentiating Conditions

Because a dilated pupil can sometimes indicate a medical emergency, doctors must rule out other conditions. Your specialist has performed tests to rule out these more serious emergencies—here is how they know you have HAS and not something else:

Condition Distinguishing Feature from HAS
Third Nerve Palsy Often includes a drooping eyelid (ptosis) and double vision. This can be an emergency requiring immediate imaging, which does not fit the slow, isolated pupil changes of HAS [3].
Horner’s Syndrome In Horner’s, the smaller pupil is the abnormal one, and it is often accompanied by a slightly drooping eyelid [8].
Pharmacological Anisocoria Occurs when a chemical or medication (like certain motion sickness patches) accidentally gets in the eye, causing the pupil to dilate. This pupil will not constrict even when strong pupil-shrinking eye drops (like 1% pilocarpine) are applied [9].
Argyll Robertson Pupil Usually affects both eyes and is almost always associated with late-stage syphilis. The pupils are typically small and irregular, unlike the large pupil in early HAS [5].

Related Autonomic Syndromes

HAS is part of a spectrum of conditions involving the autonomic nervous system (the system that controls involuntary functions) [10].

  • Ross Syndrome: This is defined by a triad of symptoms: the tonic pupils and reflex loss of HAS, plus anhidrosis (the inability to sweat) in certain parts of the body [11][12]. People with Ross syndrome may sweat excessively in other areas to compensate [13].
  • Harlequin Syndrome: This involves sudden flushing and sweating on only one side of the face or body, often triggered by exercise or heat [11].

If you are unsure how these symptoms led to your diagnosis, you can review the specific tests on the Diagnosis and the Pilocarpine Test page, or return to the Home Page.

Common questions in this guide

Why is one of my pupils larger than the other?
In Holmes-Adie Syndrome, one pupil may become significantly larger, especially in bright light. This happens because the affected pupil fails to constrict normally when exposed to light, though it often still shrinks when you focus on something close up.
Will missing reflexes affect my ability to walk or drive?
No, the loss of deep tendon reflexes in Holmes-Adie Syndrome does not affect your daily life. While your involuntary reflexes like the knee-jerk may be missing, your voluntary muscle control for walking, driving, and balancing remains completely normal.
How do doctors know my pupil changes aren't a medical emergency?
Doctors evaluate your specific pattern of pupil reactions to rule out emergencies like a third nerve palsy or Horner's syndrome. Holmes-Adie typically involves a slow, isolated pupil change without warning signs like a drooping eyelid or double vision.
What should I do if I notice changes in how much I sweat?
If you experience an inability to sweat in certain areas or notice excessive sweating in others, inform your doctor. This could indicate a related condition called Ross syndrome, which involves the typical Holmes-Adie symptoms combined with sweating abnormalities.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How can we distinguish my symptoms from more urgent conditions like a third nerve palsy?
  2. 2.Does my specific pattern of pupil reaction and reflex loss point toward an idiopathic cause or a systemic condition like Sjögren’s syndrome?
  3. 3.Should I be screened for Ross syndrome if I notice changes in how much I sweat?
  4. 4.What follow-up is needed to ensure my condition remains stable and benign?
  5. 5.Are there specific eye drops or glasses that could help with my light sensitivity and reading difficulties?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (13)
  1. 1

    Unilateral Adie's Tonic Pupil and Viral Hepatitis - Report of Two Cases.

    Karadžić J, Jaković N, Kovačević I

    Srpski arhiv za celokupno lekarstvo 2015; (143(7-8)):451-4 doi:10.2298/sarh1508451k.

    PMID: 26506756
  2. 2

    Adie-Holmes syndrome associated with COVID-19 infection: A case report.

    Kaya Tutar N, Kale N, Tugcu B

    Indian journal of ophthalmology 2021; (69(3)):773-774 doi:10.4103/ijo.IJO_3589_20.

    PMID: 33595525
  3. 3

    Pharmacologic anisocoria due to nebulized ipratropium bromide: A diagnostic challenge.

    Kokulu K, Öner H, Özen C, et al.

    The American journal of emergency medicine 2019; (37(6)):1217.e3-1217.e4 doi:10.1016/j.ajem.2019.03.047.

    PMID: 30948255
  4. 4

    A Rare Case in the Emergency Department: Holmes-Adie Syndrome.

    Colak S, Erdogan MO, Senel A, et al.

    Turkish journal of emergency medicine 2015; (15(1)):40-2 doi:10.5505/1304.7361.2015.59144.

    PMID: 27437522
  5. 5

    Adie's Pupil: A Diagnostic Challenge for the Physician.

    Xu SY, Song MM, Li L, Li CX

    Medical science monitor : international medical journal of experimental and clinical research 2022; (28()):e934657 doi:10.12659/MSM.934657.

    PMID: 35304432
  6. 6

    Tonic Pupil, a Paraneoplastic Neuro-Ophtalmological Disease Associated with Occult Breast Cancer.

    Peyman A, Kabiri M, Peyman M

    The breast journal 2015; (21(5)):543-4 doi:10.1111/tbj.12451.

    PMID: 26174775
  7. 7

    Acute Isolated Near Vision Difficulty in Patients With COVID-19 Infection.

    Umapathi T, Li KZ, Chin CF, et al.

    Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society 2021; (41(3)):e279-e282 doi:10.1097/WNO.0000000000001120.

    PMID: 34415279
  8. 8

    Tonic pupil after COVID-19 infection.

    Quijano-Nieto BA, Córdoba-Ortega CM

    Archivos de la Sociedad Espanola de Oftalmologia 2021; (96(7)):353-355 doi:10.1016/j.oftale.2021.01.001.

    PMID: 34217472
  9. 9

    PUPILLOTONIA AND ADIE SYNDROME.

    Horkovičová K, Popov I, Valašková J

    Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti 2020; (76(5)):232-235 doi:10.31348/2020/33.

    PMID: 33499645
  10. 10

    Asymptomatic Severe Vagal and Sympathetic Cardiac Denervation in Holmes-Adie's Syndrome.

    Estañol B, Callejas-Rojas RC, Cortés S, et al.

    Case reports in neurological medicine 2017; (2017()):4919758 doi:10.1155/2017/4919758.

    PMID: 28428900
  11. 11

    Clinical and laboratory correlates of selective autonomic dysfunction due to Ross syndrome.

    Panda S, Verma D, Budania A, et al.

    Journal of family medicine and primary care 2019; (8(4)):1500-1503 doi:10.4103/jfmpc.jfmpc_151_19.

    PMID: 31143750
  12. 12

    Two Cases of Tonic Pupil: Ross and Ross Syndrome Plus.

    Ahmad R, Saurabh K

    Cureus 2022; (14(2)):e22305 doi:10.7759/cureus.22305.

    PMID: 35350498
  13. 13

    Clinical presentation and autonomic profile in Ross syndrome.

    Lamotte G, Sandroni P, Cutsforth-Gregory JK, et al.

    Journal of neurology 2021; (268(10)):3852-3860 doi:10.1007/s00415-021-10531-8.

    PMID: 33813643

This page explains the symptoms of Holmes-Adie Syndrome for educational purposes only. Because pupil changes can indicate medical emergencies, you should always consult a neurologist or ophthalmologist for a proper diagnosis.

Get notified when new evidence is published on Holmes-Adie syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.