What is Urrets-Zavalia Syndrome?
In 1963, an Argentinian eye doctor called Alberto Urrets-Zavalia, made an observation about 6 patients. They all had unusual symptoms including a fixed and overly expanded pupil, degeneration of the iris, adhesions between the iris and the inner part of the eye, and high eye pressure (secondary glaucoma) after surgery for a condition called keratoconus. All patients except one were given eyemedication that made the pupils relax and expand, called atropine. He proposed that this medication might have played a key role causing these symptoms.
Urrets-Zavalia Syndrome (UZS), also known as Castroviejo syndrome, is a rare, serious complication that is characterized by a permanently enlarged, non-responsive pupil after various types of eye surgery. It could also be associated with the condition keratoconus, or the use of medication that makes the pupil relax and expand after surgery. The first person to mention this condition was Castroviejo, but it was Urrets-Zavalia who studied the condition in detail.
While a type of corneal transplant surgery called penetrating keratoplasty is most often associated with this syndrome, UZS has been observed after other eye surgeries, such as deep anterior lamellar keratoplasty, Descemet stripping automated endothelial keratoplasty, cataract surgery, and various surgeries for high eye pressure. Patients usually have a pupil that doesn’t react to changes in light or focus. The symptoms typically appear 1 to 2 weeks after their surgery.
Researchers think the cause of UZS might be due to a lack of blood supply to the iris, which results in damage to the muscles that control the pupil’s size. Despite several attempts to find preventive measures, there is no currently approved treatment for UZS.
What Causes Urrets-Zavalia Syndrome?
Urrets-Zavalia syndrome (UZS) is a condition that isn’t fully understood yet, but there are several things that researchers think might increase the risk of developing it:
* High pressure in the eye during or after surgery
* Using drugs that widen the pupils during or after surgery
* Having keratoconus, a disease that changes the shape of your cornea (the clear front part of your eye)
* Leaving a specific type of surgical material (viscoelastic material) in the front part of your eye after surgery
* Injecting air or gas into the front part of your eye
Inflammation in the front part of your eye, possibly due to surgery, is also believed to be a risk factor.
However, these risk factors aren’t agreed on by everyone since the data and reports on UZS are limited and sometimes conflicting. UZS has been observed following several different types of eye surgeries. For example, this includes surgeries to replace the cornea (like penetrating keratoplasty and DALK for conditions like keratoconus), surgeries to replace certain layers of the cornea (like Descemet stripping endothelial keratoplasty or DMEK for conditions like bullous keratopathy and corneal edema), and various other interventions such as using an intracameral gas injection for acute corneal hydrops, or implanting an intraocular lens.
In some cases, other complications following these surgeries—like high eye pressure after surgery, needing further surgery due to graft dislocation, or inflammation in the eye—might lead to symptoms of UZS.
Cataract surgeries (small incision cataract surgery, phacoemulsification, and conventional extracapsular cataract extraction) that lead to toxic anterior segment syndrome (TASS) have also been associated with UZS. UZS and TASS might even be different stages of the same thing. It has been noted that UZS can develop a few weeks after certain types of cataract surgeries.
Surgeries like trabeculectomy or combined trabeculotomy and trabeculectomy for glaucoma, minimally invasive glaucoma surgery, and others have also been linked with UZS. Similarly, artificially dilating the pupil in patients with pigment dispersion syndrome, or injecting cidofovir (a drug) into the veins in people with low eye pressure, may cause UZS.
However, it’s important to note that exactly how these factors lead to UZS isn’t clearly understood yet, and might depend on individual circumstances.
Risk Factors and Frequency for Urrets-Zavalia Syndrome
Urrets-Zavalia syndrome is quite rare and unpredictable, with reported occurrence rates anywhere from 0% to 17.7% following a specific kind of eye surgery called penetrating keratoplasty. This wide range may be due to different ways to diagnose the condition, missed diagnoses, and a mild form of the syndrome where the pupil returns to normal size over time. Current research does not provide a clear overall rate of occurrence.
The syndrome seems to affect males and females equally and can occur at any age, although it’s still unclear if it occurs more frequently in certain age groups or genders. Usually, it affects only one eye, even if surgery was done on both. However, cases where it affects both eyes have been reported in patients with a specific eye condition known as macular corneal dystrophy who underwent penetrating keratoplasty. This could indicate irregularities with the iris or a muscle in the eye called the sphincter pupillae.
Signs and Symptoms of Urrets-Zavalia Syndrome
Urrets-Zavalia syndrome is a condition where a person’s pupil does not react to light, does not accommodate, and is resistant to pilocarpine treatment. It usually becomes noticeable within the first 1 to 2 weeks after a cornea transplant, though it can also occur up to 5 months after surgery. People with this syndrome may experience glare, halos, sensitivity to light, and potentially elevated eye pressure. It can cause damage to the optic nerve, which is commonly associated with glaucoma.
A slit-lamp exam, a test that checks the health of your eyes, could show that the front and back layers of the iris (the coloured part of your eye) have thinned out. It could also reveal that the iris has attached to the lens of the eye or that white, dotty lesions, known as glaukomflecken, have formed. These changes can lead to the development of acute angle-closure glaucoma, a severe type of glaucoma.
- Unreactive pupil
- Experiences glare, halos, and light sensitivity
- Potential elevated eye pressure and optic nerve damage
- Thinning of iris layers
- Potential glaukomflecken
- Possible acute angle-closure glaucoma
The incomplete and temporary versions of Urrets-Zavalia syndrome could show thinning of the front layer of the iris and pigment spots on the inside lining of the cornea and the front capsule of the lens. Other signs of it could be a weakened cornea, the iris attaching to the lens, pigment depositing on the front surface of the lens, and the cornea’s inner cell layer. Also, your doctor may find indications of iris ischemia, a condition where the blood supply to the iris is interrupted or decreased. They may even observe transillumination defects, areas where light passes directly through the iris due to thinning. In severe cases of Urrets-Zavalia syndrome, the pupil does not constrict, even after the application of pilocarpine 2% or 4% eye drops, typically used to treat glaucoma.
Testing for Urrets-Zavalia Syndrome
Your doctor will first get a complete medical and surgical history from you, and even check whether you’re taking any medications that might affect your eyes. This is done because certain drugs can make the pupil of your eye bigger (a condition called mydriasis).
Your vision will be tested and your doctor will check your eyes, including the pressure inside your eyes, and how well your pupils react to light.
There’s a condition called Urrets-Zavalia syndrome that can potentially lead to a severe complication known as acute-angle closure glaucoma, which is a type of eye condition that can cause blindness. If the doctor suspects you might have Urrets-Zavalia syndrome, they might examine your eye using a special instrument called a slit lamp to see it more clearly.
After this, the doctor may use another method called gonioscopy to check the front part of your eye for any abnormal tissue sticking. If gonioscopy doesn’t provide enough details, the doctor may use ultrasound biomicroscopy (UBM). This is an ultrasound technique that gives a more detailed view of the small structures in the front part of your eye.
Depending on the case, your doctor may also use other tests such as corneal tomography (which displays the shape of the cornea, the clear front surface of your eye), optical coherence tomography (which makes an image of your eye to check things like corneal thickness and the optic nerve), and anterior segment fluorescein angiography (which uses a special dye to illuminate the blood vessels in the front part of your eye).
Finally, a specific test called anterior segment indocyanine green angiogram can show a delay or decrease in the filling of the blood vessels in the iris (colored part of your eye). This indicates a lack of sufficient blood supply to the iris, suggesting it plays a critical role in causing Urrets-Zavalia syndrome.
Treatment Options for Urrets-Zavalia Syndrome
Urrets-Zavalia syndrome is a condition that doesn’t have a definitive treatment at this point. The current approaches to treat this syndrome rely on medications like dapiprazole and guanethidine drops, which can help to shrink the pupil, a condition known as miosis. Some studies have suggested that these medicines can effectively treat symptoms such as involuntary muscle spasms in the iris (colored part of the eye) and miosis. However, we need more research to determine how safe and effective these medicines truly are. Moreover, it’s very important to manage eye inflammation and regulate the pressure inside the eye.
Surgical treatments are only considered in cases where the iris touches the cornea and the front part of the eye is too shallow. These procedures can help to disconnect the adhesions (clumps of scar-like tissues) inside the eye and restore its normal structure. Other surgical options include modifying the pupil’s shape and size to manage severe sensitivity to light that can’t be controlled by sunglasses or other precautions. Corneal tattoos, special contact lenses, and intraocular lenses are also used to control this sensitivity. If the pressure inside the eye needs to be reduced, surgery for glaucoma might be required. In some cases, a procedure to rebuild the front part of the eye might also be necessary.
To prevent Urrets-Zavalia syndrome, several measures can be taken. Prior to any eye surgery, diabetic drugs like mannitol can be injected to decrease the volume of a jelly-like substance in the eye called vitreous humor and prevent constriction of the iris due to a sudden increase in the eye’s pressure. A type of laser treatment, known as YAG laser iridotomy, can also be performed before surgery to lower the eye pressure. During the surgery, the surgeon must be careful to avoid damaging the iris and should ensure the front part of the eye is deep enough. Any substances used during surgery that help maintain the shape of the eye should be completely removed afterwards to prevent toxic reactions from residues. Although some doctors suggest creating a hole in the iris during surgery to prevent blockage and iris constriction, others are uncertain about its effectiveness in preventing Urrets-Zavalia syndrome.
The syndrome may be linked with the use of air or gas in the eye, specifically during certain procedures. Therefore, it is important for doctors to use these substances cautiously and consider using drugs like mannitol. Although it’s unclear whether medications used to reduce eye pressure before the surgery can help prevent Urrets-Zavalia syndrome, there’s debate about the role of medications used after surgery to dilate the pupil. Some suggest these drugs might even contribute to the development of this syndrome. In spite of this, it’s usually advised to avoid strong pupil dilating medications and instead consider using short-acting drugs on alternate days.
What else can Urrets-Zavalia Syndrome be?
When a patient has a wide and unresponsive pupil after eye surgery, it’s important to explore all potential causes. These might include:
- Sudden glaucoma where the eye’s fluid is blocked
- Anterior uveitis, a type of eye inflammation
- Posterior synechiae, when the iris sticks to the lens of the eye
- Pupillary block, another form of glaucoma
- Neurogenic syphilis which affects the brain and nervous system
- Unintentional damage to the iris during surgery
- A pupil that is dilated due to an injury (traumatic mydriasis)
- Adie pupil, a neurological disorder affecting the eye
- A pupil that is dilated because of certain medications (pharmacologic mydriasis)
- A condition impairing eye muscle movements (third nerve palsy)
These conditions have similar symptoms, so it may be difficult to determine the exact cause immediately. Therefore, a thorough investigation is necessary to make a correct diagnosis.
What to expect with Urrets-Zavalia Syndrome
About 30% to 70% of people with Urrets-Zavalia syndrome, a condition that affects the eye’s ability to react to light, regain some form of eye function within 18 weeks of the condition starting. However, only a small portion, just about 4.8%, return to normal eye function when looking at severe cases of Urrets-Zavalia syndrome.
Some factors which may increase the chances of regaining the eye’s ability to react to light and return to normal size include the quick treatment of raised eye pressure after surgery, the eye reacting to light even when enlarged, and the eye shrinking in response to the use of a specific eye drop called pilocarpine 2%.
Unfortunately, about 30% of people do not regain movement in their eye. For these individuals who are left with a permanently enlarged pupil, a surgical procedure or other treatments might be necessary if they find light too intense or uncomfortable.
Possible Complications When Diagnosed with Urrets-Zavalia Syndrome
The main complication of a condition called Urrets-Zavalia syndrome is a severe form of glaucoma, known as acute angle-closure glaucoma. This happens because of the creation of adherences between the iris and cornea, which lead to a subsequent collapse of the front part of the eye (the anterior chamber angle). Quick recognition and diagnosis of this condition are vital to protect the patient’s optic nerve and eyesight. The treatment involves using medication to reduce eye pressure and later, surgical procedures to remove the adhesions and repair the anterior chamber.
Common Complications and Treatment:
- Main complication: Acute angle-closure glaucoma
- Causes: Adherences causing collapse of the anterior chamber of the eye
- Essential: Quick diagnosis to protect optic nerve and vision
- Treatment: Medication to lower eye pressure
- Surgical interventions: Removal of adhesions and repair of the anterior chamber
Preventing Urrets-Zavalia Syndrome
If you have Urrets-Zavalia syndrome, your doctor should discuss with you the possibility of developing a type of eye condition called acute angle-closure glaucoma. This condition causes sudden eye pain and can lead to vision loss if not treated urgently. To reduce the risk of this happening, it’s a good idea to avoid poorly lit areas. This can stop your pupils from widening excessively, which would narrow the space where fluid drains in your eye, increasing the risk of glaucoma.
There are certain medications that can make your pupils dilate, or widen, which could increase your risk of glaucoma. These medications include certain types of drugs for anxiety, depression, asthma, and certain antibiotics, so it’s very important to discuss any medication you’re taking with your doctor.
If you have Urrets-Zavalia syndrome and you’re farsighted (hypermetropia), your doctor should also explain that you have a higher chance of developing angle-closure glaucoma. This is because the structure of your eye might have a shallower space where fluid drains, or the lens of your eye might be located more towards the front, both of which can result in a higher risk of glaucoma.
