What is Adie Syndrome (Holmes-Adie Syndrome)?
Adie syndrome, also known as Holmes-Adie Syndrome, is named after two neurologists – William John Adie, from Australia, and Sir Gordon Morgan Holmes, from Ireland. The condition was first named and reported by them in 1931. In fact, previous descriptions of the syndrome can be traced back to as early as 1881.
This neurological disorder, which causes a condition known as a tonic pupil, is fairly common. A tonic pupil is one that is abnormally large and responds slowly to light. We don’t yet know exactly what causes Adie syndrome, which can affect one or both pupils. This disorder also causes loss of reflexes and can disturb normal bodily functions related to blood vessels and sweat glands. It is also more common in women.
Patients with this condition may experience shrinking of the pupils over time, an increasing chance that both pupils will be affected each year, and loss of deep tendon reflexes. Sometimes, the syndrome can be linked to hypohidrosis, a condition marked by decreased sweating. When the two are connected, it’s known as Ross syndrome.
What Causes Adie Syndrome (Holmes-Adie Syndrome)?
Adie syndrome usually occurs without a clear reason. However, in some rare cases, it can be caused by issues affecting a part of the eye called the ciliary ganglion. These might include infections from certain viruses or bacteria, such as syphilis, chickenpox, parvovirus B19, HIV, and Lyme disease. Other possible causes include a lack of blood flow due to conditions like lymphomatoid granulomatosis, migraine, and giant cell arteritis, or autoimmune disorders like Sjogren syndrome, polyarteritis nodosa, sarcoidosis, lupus, amyloidosis, Guillain-Barre syndrome, and Vogt-Koyanagi-Harada disease.
Adie syndrome might also be linked to heart conditions, anesthesia, eye and eye area tumors, surgery for broken bones in the eye area, nerve and muscle conditions like Lambert-Eaton myasthenic syndrome, and diseases linked with anti-Hu antibodies. Some causes might be related to damage to ciliary nerves in the suprachoroidal space, a part of the eye, due to retinal photocoagulation – a laser treatment to seal leaky blood vessels in the eye. It is also sometimes seen in people with familial dysautonomia, a genetic disorder affecting the nervous system.
Recently, there have been reports of two cases where Adie syndrome was linked with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This may be because the virus can directly invade the ciliary nerves or ganglion in the eye, or due to a delayed reaction caused by the immune system.
Risk Factors and Frequency for Adie Syndrome (Holmes-Adie Syndrome)
Adie syndrome happens rarely, with each year having about 4.7 cases in 100,000 people. On average, about two in every 1,000 people has it. It’s most often seen in young adults between the ages of 25 to 45, with 32 being the average age people have it. More women have it than men, with the ratio being 2.6 to 1. It usually only affects one side of the body in 80% of cases. Cases where it runs in families are hardly ever reported. The exact number of people who have it or get it each year is still unknown.
- About 4.7 in 100,000 people get Adie syndrome each year.
- Out of 1,000 people, around two will have it.
- It’s most common in young adults aged 25 to 45, with the average age being 32.
- The majority (about 2.6 out of every 3.6) of cases are females.
- It’s sporadic and mostly occurs in families rarely.
- It generally affects only one side in 80% of cases.
- The exact number of people with Adie syndrome or who get it each year is still unclear.
Signs and Symptoms of Adie Syndrome (Holmes-Adie Syndrome)
Adie syndrome is a condition that shows up with several characteristics. A patient may have one pupil that is larger than the other, which reacts poorly or not at all to light changes. They may experience sweating abnormalities, particularly seen in Ross syndrome. This condition is often associated with a diminished or complete loss of certain reflexes, notably in the Achilles tendon.
Patients might find it hard to read and could also be sensitive to bright light. Other possible signs include increased farsightedness, varying levels of nearsightedness and farsightedness between the two eyes, partial paralysis of the pupil controlling muscle, exaggerated reaction to nerve stimulation in muscles where the nerves have been damaged, and low blood pressure when standing up. In some instances, Adie syndrome might be associated with a chronic cough. Diseases such as infections, autoimmune diseases, or cancers may also show similar signs and symptoms.
We’ll list these symptoms and signs below for clarity:
- One pupil larger than the other
- Poor pupillary reaction to light
- Sweating abnormalities
- Reduced or lost Achilles tendon reflex
- Difficulty in reading
- Sensitivity to bright light
- Increased farsightedness
- Different nearsighted and farsighted levels in each eye
- Partial paralysis of pupil controlling muscle
- Exaggerated reaction to nerve stimulation in muscles
- Low blood pressure when standing up
- Chronic cough
- Signs and symptoms of associated conditions (i.e., infections, autoimmune diseases, and cancers)
Testing for Adie Syndrome (Holmes-Adie Syndrome)
The Adie pupil is a specific eye condition that is characterized by a strong response to nearby images or objects, followed by a slow and enduring relaxation of the iris. This phenomenon is due to unusual behavior and sensitivity of the eye’s muscles to certain stimulants like pilocarpine, a medication used to treat glaucoma. Over time, the affected pupil, which is usually larger than its counterpart, tends to shrink, creating what’s known as the “little old Adie pupil”. This smaller version of the Adie pupil can be identified by its weak response to light and unusually strong response to nearby stimuli.
Although usually affecting only one eye, in rare instances (about 20% of Adie pupils), both eyes are affected. Notably, bilateral cases of the condition increase by about 4% per year. If you have a difference in pupil size of more than 1 millimeter, or if paralysis in a certain section of the eye is detected during a slit-lamp examination, it could distinguish Adie syndrome from other general nerve problems that cause wide pupils.
Moving towards diagnosis, Adie’s syndrome is typically diagnosed clinically. However, the pupil’s unusual hypersensitivity can be demonstrated with a special test using a low-concentration pilocarpine, a type of medication. What’s important to note here is that only the affected eye will respond to such a low concentration of this medication. However, it’s important not to rely solely on this test for diagnosis since there are other conditions, like third nerve palsy, that may show similar results.
Additional tests, such as the starch iodine test or the spoon test, are used to rule out other syndromes like Ross or harlequin syndromes, as these tests help detect the absence of sweat.
Finally, several medical conditions that might mimic or cause Adie syndrome need to be ruled out. These include syphilis, diabetes, chronic alcoholism, encephalitis, multiple sclerosis, peripheral nerve disease such as Charcot-Marie-Tooth, rare midbrain tumors, herpes zoster, and a condition called neurosarcoidosis. However, the specific set of tests would vary for each person depending on the accompanying symptoms. Sometimes, computed tomography and magnetic resonance imaging scans could be useful in testing for reflexes that aren’t working properly.
Treatment Options for Adie Syndrome (Holmes-Adie Syndrome)
For most people with Adie syndrome, a condition where nerves are damaged primarily in the eyes and skin, there is no need for specific treatment. If Adie syndrome is connected to another condition affecting the nerves, that condition should be treated.
When Adie syndrome affects the eyes (making it hard for them to adjust or focus), reading glasses are commonly prescribed. Eye drops containing pilocarpine or physostigmine can also be used both for treatment and to help diagnose the condition.
If these approaches don’t work and the person experiences excessive sweating (diaphoresis), a type of surgery called a thoracic sympathectomy might be considered as the preferred treatment option.
What else can Adie Syndrome (Holmes-Adie Syndrome) be?
When doctors are trying to diagnose Adie syndrome, they have to rule out various other conditions that can show similar symptoms. One such condition is Argyll Robertson pupil, found in the late stages of syphilis, which is associated with miosis (constricted pupils).
- Other causes could include chemical dilation of the pupil, which would also fail the light-near test, where pupils do not react properly to light and focus.
- Oculomotor nerve palsy can have similar symptoms. This is a nerve condition that can cause eye movement difficulties and drooping eyelids.
- Diseases affecting the optic nerve can also be a cause, presenting with a diminishing vision and irregular pupil response to light.
Conditions like Ross and harlequin syndromes, which are nerve disorders affecting different areas of the body, can influence the ciliary ganglion in the eye and cause a tonic pupil, which is a hallmark of Adie Syndrome.
- Ross syndrome is characterized by a tonic pupil, reduced reflex response, and segmental anhidrosis — a condition that prevents sweating in certain body regions.
- Harlequin syndrome is a rare disorder characterized by unilateral flushing and sweating complications, often exaggerated on the unaffected side, particularly on the face, neck, arm, and chest. These reactions are usually triggered by heat, exercise, or emotional factors.
Horner’s syndrome is another condition to consider. This can cause a miotic pupil, as well as ptosis (drooping of the upper eyelid) and the sense of the eye receding into the socket. Miosis or constricted pupils could also be an early sign after a head injury due to overload in the brain. Constricted pupils can occur due to irritation to the oculomotor nerve responsible for controlling the size of the pupils. However, this is usually followed by pupil dilation.
What to expect with Adie Syndrome (Holmes-Adie Syndrome)
Adie syndrome is not a condition that worsens over time, nor is it life-threatening or disabling. It doesn’t have a connection to any death rate. However, it does involve permanent loss of deep tendon reflexes that may become more pronounced as time goes on.
Mostly, patients just need reassurance once the diagnosis has been confirmed. There have been infrequent links between angle-closure glaucoma and Adie syndrome; however, these instances are not common.
Over time, the symptoms connected to Adie syndrome, such as accommodative paresis, generally improve on their own. But with time, the pupil’s response to light may become weaker and the pupils may shrink, a phenomenon often referred to as “little old Adie”.
Possible Complications When Diagnosed with Adie Syndrome (Holmes-Adie Syndrome)
Adie syndrome is a rare condition that can occasionally lead to a type of glaucoma. This causes the vision to go blurry and discomfort in the eyes. Treating it involves both medication to reduce the pressure inside the eye and a laser procedure to avoid blockage in the iris, the colored part of your eye.
This syndrome has also been known to cause a condition in children called amblyopia. This happens when the eye’s focusing power, hypermetropia, changes from latent (hidden) to manifest (apparent), due to weakened muscle control. Luckily, this condition can be effectively managed by correcting the eye’s ability to focus with glasses and providing an eye patch treatment.
Preventing Adie Syndrome (Holmes-Adie Syndrome)
Patients should be comforted in knowing that this medical condition is usually not serious. However, those who are at higher risk should be aware that they might develop angle-closure glaucoma. They should be informed about what this entails, its symptoms, and the factors that can trigger it.
Parents with children who have Adie syndrome should understand how vital regular check-ups are for their child. Regular monitoring can help catch vision problems like refractive defects and anisometropia early. If left untreated, these issues can lead to amblyopia, a condition that can affect a child’s vision.
