Pseudoexfoliation Syndrome and Glaucoma

What is Pseudoexfoliation Syndrome and Glaucoma?

Pseudoexfoliation syndrome (PEX) is a condition that causes a buildup of extra material in various parts of the eye. Generally affecting those over the age of 60, PEX is often seen during regular eye exams when white flaky material, similar to dandruff, is seen on the iris (the colored part of your eye) and the lens (the part of your eye that helps focus light onto the retina). This condition is normally noticed in routine eye check-ups and shows more frequently in individuals over 60.

This extra material can accumulate on the lens, the iris, and the ciliary body (a part of the eye that produces fluid). This may increase eye pressure, leading to a special type of glaucoma known as pseudoexfoliative glaucoma. PEX can also raise the risk of cataracts (clouding of the eye lens). While there’s no cure for PEX as of now, spotting it early can help slow down any related vision loss.

The term ‘Pseudoexfoliation’ and its unique traits were first brought to light in 1917 and became more understood in the 1950s. Initially, it was thought to be a harmless change in the eye due to aging. However, further studies showed it has a higher risk of causing glaucoma and other vision problems. The reason why PEX happens is still not known definitively.

PEX may occur in one eye or both and is among the most common identifiable causes of secondary open-angle glaucoma, a condition characterized by an increase in eye pressure. PEX can lead to complications like capsular bag rupture (a thin membrane that holds the lens in place ruptures), zonular dialysis (separation of the zonule that holds the lens in place from the ciliary body), and loss of vitreous, the clear gel that makes up most of the eye’s interior. These complications can arise during cataract surgery, making the procedure more challenging.

What Causes Pseudoexfoliation Syndrome and Glaucoma?

PEX is a condition where white, flaky deposits form on the lens and iris of the eye. This can lead to several eye problems, such as cataracts, glaucoma, and issues with the layer of cells at the back of the cornea. It’s not exactly clear what causes PEX, but certain genes might make some people more likely to develop it based on genetic studies.

Some specific genes that may contribute to PEX are:
– A gene called Lysyl oxidase-like 1 (LOXL1), which is involved in connecting collagen and elastin fibers, substances that make tissues flexible but strong. Changes in this gene have been linked to PEX in several populations worldwide.
– The Clusterin (CLU) gene, which helps prevent unwanted protein buildup. In PEX cases, there can be a depletion in Clusterin leading to abnormal accumulations.
– The Calcium Voltage-Gated Channel Subunit Alpha 1 (CACNA1A) gene potentially influences the calcium levels that might be related to PEX.
– The Glutathione transferase (GST) gene which helps protect cells from harm due to unchecked oxidation. Some alterations to this gene have been noticed in Pakistani patients with PEX but not in other groups.
– Down regulation, or decreased functionality, of the Fibulin-5 (FBLN5) gene has been linked to the risk of developing PEG, a condition related to PEX.

However, it’s not just genetics that can potentially cause PEX. Environmental factors like sunlight exposure, excessive alcohol or caffeine intake, certain climates and diets, viral infections and eye surgeries can also influence its development. Specifically, these factors increase oxidative stress, disrupt the balance between antioxidant defense mechanisms and production of ‘free radicals’ – unstable molecules that can damage cells.

The flaky deposits, made of different proteins and enzymes, in affected individuals’ eyes can limit the eye’s drainage system and increase internal eye pressure, evolving into PEG, a specific type of glaucoma. PEG is triggered by the progressive build-up of PEX, and if not treated, can lead to blindness. Red flags of this kind of glaucoma are irreversible damage to the optic nerve and retina, usually progressing more rapidly than in other types of glaucoma.

Risk Factors and Frequency for Pseudoexfoliation Syndrome and Glaucoma

PEX, or pseudoexfoliation syndrome, is a condition that most commonly affects people over the age of 60, with studies suggesting that up to 20% of this age group might have it. The occurrence of PEX can vary greatly in different geographical regions, with reported rates ranging from 0 to 38%. Notably, people of Scandinavian, Northern European, and Mediterranean descent are more likely to have PEX, particularly in Nordic and Eastern Mediterranean countries. On the other hand, East Asian populations and the Inuit people of Greenland report the lowest prevalence of PEX. Factors like genetics, diet, climate, exposure to sunlight, and proximity to the equator may all contribute to this variation.

• The risk of developing PEX increases with age, and it is rarely seen in people under 50.
• People from Nordic and Eastern Mediterranean regions have a higher risk.
• High altitude and exposure to solar or cosmic radiation can also increase the risk.
• The condition might be more common in females, although recent studies have found roughly equal rates in males and females.
• Lifestyle factors, such as a diet low in antioxidants, smoking, and alcohol consumption, can also contribute to the risk.

When an individual with PEX develops persistently high or unstable eye pressure, along with changes in vision or damage to the optic nerve, they may be diagnosed with secondary glaucoma, or PEG. PEG is responsible for 25% of all open-angle glaucoma cases worldwide. The risk of a person with PEX developing PEG over a decade is about 15%. PEG can cause progressive damage to the nerve cells in the retina, leading to permanent loss of peripheral vision.

Signs and Symptoms of Pseudoexfoliation Syndrome and Glaucoma

PEX and PEG are eye conditions that can be diagnosed during a detailed eye exam. The key sign of PEX is flaky whitish deposits seen on the lens and iris of the eye, while an increased intraocular pressure, or IOP, indicates PEG. Some patients may not show any symptoms, while others might experience a loss of peripheral vision due to secondary glaucoma or PEG. Diagnosing these conditions require a thorough eye exam that leverages tools like a slit lamp for direct visualization of the eye and gonioscopy for examining the eye’s drainage angle.

The slit lamp examination reveals white, flaky deposits on the lens and iris, looking similar to dandruff. These deposits concentrate around the edges of your eye’s pupil and on the front part of your lens. Sometimes, conditions can resemble PEX, like the presence of pigment deposits causing a line known as a Krukenberg spindle, or the misinterpretation of PEX deposits as inflammation debris. In some cases, the front part of your eye may appear less clear due to the accumulation of PEX material and damage to your iris, which affects the width of your pupil.

Additionally, there can be further complications such as weak connections between your eye’s lens and the tissues supporting it, often causing your lens to shift from its correct position. Studies also found a higher occurrence of certain types of cataracts in eyes affected by PEX, though the root cause is not yet known.

Gonioscopy, or examining the eye’s drainage angle, is another crucial part of the examination for PEX. It helps in identifying PEX deposits and hyperpigmentation, an increased amount of pigment, over certain structures in the eye. Gonioscopy can give critical clues about identifying PEX even in cases where it affects only one eye.

• Flaky whitish deposits on the lens and iris
• Increased intraocular pressure
• Loss of peripheral vision (in some cases)
• Pigment deposits forming a line known as a Krukenberg spindle
• Weak connections between the eye’s lens and the supporting tissues
• Higher occurrence of certain types of cataracts
• PEX deposits and hyperpigmentation in the eye

Testing for Pseudoexfoliation Syndrome and Glaucoma

If you are suspected to have pseudoexfoliation syndrome (PEX), a type of eye abnormality that affects the natural proteins in the eye, your doctor will perform a detailed eye exam and use a special microscope known as a slit-lamp. They will also measure your baseline eye pressure, as people with PEX are at a high risk of developing high eye pressure and a condition called pseudoexfoliation glaucoma (PEG). Eye genetics tests are typically not performed for PEX, as the diagnosis is often based on clinical evaluation.

The process of evaluating patients suspected of having PEG is the same as for those suspected of having primary open-angle glaucoma (POAG), the most common type of glaucoma.

The clinical evaluation involves:

Visual examination of the back of your eye: The doctor will use a slit lamp and a special lens to magnify your eye. They’ll look for signs of damage related to glaucoma, such as an increased cup-to-disc ratio (a measure of the size of the optic nerve), cupping or hollowing of the optic nerve, and bleeding around the optic nerve.

Eye pressure measurement: High eye pressure is often associated with pseudoexfoliation and can vary throughout the day. Therefore, your eye pressure should be checked at multiple different times. Even though Goldmann applanation tonometry is the standard method for measuring eye pressure, your doctor will also consider the impact of cornea thickness on the measurement.

Field of Vision Analysis: This test helps detect areas of vision loss. Commonly, a computerized visual field test is used, which maps out the full horizontal and vertical range of what you see peripherally without moving your eyes. With Pseudoexfolation Glaucoma, it’s typical for there to be vision loss and it tends to get worse faster than with other types of glaucoma.

Optical coherence tomography (OCT): This non-invasive imaging test helps to visualize the nerve fibers in your retina, the light-sensitive tissue at the back of your eye. Thinning of these nerves is associated with glaucoma. The pattern of thinning can be used to detect early glaucoma or differentiate severe glaucoma from healthy eyes.

Treatment Options for Pseudoexfoliation Syndrome and Glaucoma

Currently, there’s no way to stop the accumulation of PEX material in eyes affected by this condition. The best way to manage it is to have regular eye exams (at least every year), which can help catch and treat glaucoma early.

One of the commonly used treatments for PEG involves eye drops that lower eye pressure. These might include prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, or a combination of them. Pilocarpine is not recommended due to the risk of making angle-closure glaucoma worse and the formation of posterior synechiae. PEG tends to be more resistant to medication than POAG. The target eye pressure should be quite low in people with PEX to help manage the risk of progression.

Laser treatment can also be utilized for the management of PEG. This method may be the first line of treatment or used to prevent more invasive surgery. One type of laser treatment, selective laser trabeculoplasty (SLT), can successfully reduce eye pressure by 30% in PEG patients. However, the effects of SLT are not permanent, and more surgeries may be needed in the long run.

While surgical treatment is an option for the management of PEG, it’s often only considered when medications and/or laser treatment are not working. Surgeries such as trabeculectomy, glaucoma drainage devices, canaloplasty, and viscocanalostomy can be performed. However, post-operation, there might still be a need to use eye drops to help manage pressure in the eye. Laser iridoplasty or cataract extraction may also help if there’s a component of angle closure due to a cataract or anterior lens movement.

The surgical removal of a cataract can be challenging in PEX patients because it can cause a wide range of problems like poor mydriasis, instability of the zonules, and lens subluxation. There might also be an increase in postoperative complications, so PEG patients often need a more aggressive and prolonged post-operative steroid treatment. That’s why it’s crucial to examine all eyes that are undergoing cataract extraction for pseudoexfoliation to help plan and follow-up with the surgery.

New treatments for PEG are always being researched. They are being tested in preclinical and animal models and include methods like magnetic phage display, gene therapies, stem cell therapy, nanotechnology, immunotherapy, and photobiomodulation.

What else can Pseudoexfoliation Syndrome and Glaucoma be?

Pigment dispersion syndrome, true exfoliation of the lens capsule, amyloidosis, primary open-angle glaucoma, and primary angle-closure glaucoma can be mistaken for Pseudoexfoliative syndrome (PEX) because they all lead to changes in the eye, but there are ways to distinguish between them.

• Pigment dispersion syndrome: This condition is similar to PEX in that it causes changes in the cornea of the eye. However, it further causes mid-peripheral atrophy, or waste away on the iris compared to the pupillary border defects in PEX. On inspection, the iris seems to bend backward, and the coloration in the mesh-like tissue in the eye (trabecular meshwork) is more uniform than the patchy coloration seen in PEX.
• True exfoliation of the lens capsule: This is a rare condition where exposure to infrared radiation causes the superficial and deeper layers of the front part of the lens cover to separate. Upon examination, it shows a thin white layer coming out from the eye lens into the front chamber of the eye.
• Amyloidosis: The build-up of abnormal proteins called amyloids can look like PEX material and deposit within the front section of the eye.
• Primary open-angle glaucoma: Unlike PEX, there are no signs of white, flaky deposits on the front section of the eye.
• Primary angle-closure glaucoma: The intraocular pressure (pressure inside the eyes) increases due to angle closure without the presence of PEX material.

What to expect with Pseudoexfoliation Syndrome and Glaucoma

PEX, short for Pseudoexfoliation Syndrome, has a significant connection to the development of glaucoma, a condition that can damage your eye’s optic nerve. Research has shown that 44% of those diagnosed with PEX ended up developing high eye pressure that needed treatment or glaucoma within 15 years.

Additionally, if one eye is affected by PEX, there’s a 29% chance that the other eye will show evident PEX within the same 15 years. When comparing PEX with POAG (Primary Open-Angle Glaucoma, a common type of glaucoma), eyes affected by PEX tend to have higher intraocular pressure – a term that basically refers to the fluid pressure inside the eyes. This pressure also tends to change more throughout the day.

Worryingly, the damage to the optic nerve tends to progress quickly in PEX, and as a result, the subsequent loss of visual field (basically, the total area that can be seen without moving the eyes) might be worse than those with POAG.

Possible Complications When Diagnosed with Pseudoexfoliation Syndrome and Glaucoma

Eyes with Pseudoexfoliation (PEX) syndrome may deteriorate over time, leading to higher eye pressure or potentially to glaucoma, a severe eye condition. Another concern in such cases is the increased complexity of cataract surgeries. Some issues that can worsen the surgery include: damaged cells on the inner surface of the cornea, poor pupil dilation, dislocated lens, and instability of the fiber-like structures that hold the lens in place.

Issues encountered after cataract surgery range from:

• Swollen cornea due to fluid build-up
• Barrier between the blood and the clear front portion of the eye doesn’t work properly
• Clouding of the lens envelope
• Increased eye pressure
• Narrowing of the opening in the lens envelope
• A high amount of inflammation
• Severe damage to the fiber-like structures that hold the lens
• Rupture of the lens envelope
• Leakage of blood vessels in the iris (the colorful part of the eye)
• And late displacement of the artificial lens inserted during cataract surgery

People with PEX and its glaucoma version (PEG) generally need closer monitoring and stronger treatments whenever the eye pressure increases and there are signs of worsening glaucoma.

Preventing Pseudoexfoliation Syndrome and Glaucoma

Patients should have eye exams every year to catch high eye pressure (ocular hypertension) or glaucoma in the early stages. People who are taking medication to treat these conditions should be aware that sticking to the recommended treatment helps prevent the conditions from getting worse. Those who need cataract surgery should be made aware that the surgery can have risks and complications, and might require additional surgeries. They should also understand that there is a chance that their intraocular lens (IOL, a lens implanted in the eye during cataract surgery) might shift position even years after the surgery.

Also, PEX, a condition characterized by protein-like substances building up in the body’s tissues, has been strongly linked to heart and brain diseases. Because of this association, patients might be encouraged to work with their main doctor to address potential risk factors related to blood vessel health.