Exfoliation Glaucoma

exfoliative glaucoma, pseudoexfoliation glaucoma, pseudoexfoliative glaucoma

Exfoliation glaucoma is the most common identifiable form of secondary open-angle glaucoma worldwide, affecting an estimated 5 to 6 million people globally. This serious eye condition develops when abnormal protein material accumulates in the eye’s drainage system, leading to elevated pressure and potentially severe vision loss if left untreated.

Table of contents

• What is Exfoliation Glaucoma?
• Who is Affected?
• What Causes This Condition?
• Signs and Symptoms
• How is it Diagnosed?
• Why Early Detection Matters
• Treatment Options
• Connections to Overall Health

What is Exfoliation Glaucoma?

Exfoliation glaucoma develops in some patients with a condition called exfoliation syndrome (also known as pseudoexfoliation syndrome). This form of glaucoma is caused by the abnormal accumulation of protein in the drainage system and other structures of the eye^[1]. This is a type of open-angle glaucoma, which means the drainage angle of the eye remains open but becomes blocked by abnormal material^[1].

The condition involves the production and gradual buildup of an abnormal fibrillar protein material on various structures in the front part of the eye, including the lens surface, iris, and most importantly, the eye’s drainage channels called the trabecular meshwork^[3]. When this flaky material, along with pigment that is released from the iris, blocks the outflow of fluid from the eye, pressure inside the eye increases, which can damage the optic nerve and cause glaucoma^[5].

Not all people with exfoliation syndrome develop glaucoma. However, if you have exfoliation syndrome, your chances of developing glaucoma are about six times higher than people who do not have it^[5]. Studies suggest that approximately 40% of patients who have exfoliation syndrome will develop glaucoma^[2].

Who is Affected?

Exfoliation glaucoma is considered a disease of the elderly^[3]. It typically presents after 60 years of age, and the condition’s incidence increases with age^[2][3]. The estimated global number of individuals with exfoliation glaucoma varies between 5 and 6 million^[3].

The prevalence of exfoliation syndrome varies significantly depending on geographic location and population. It is more common in certain ethnic groups including people from Russia, the Nordic countries, Greeks, Mediterranean populations, Indians, and others^[1]. The condition is classically described in Scandinavian populations but is also common elsewhere in Europe as well as in the Middle East, Southeast Asia, India, South Africa, and South America^[2]. Both men and women are equally affected^[2].

Although risk factors such as high altitude, diet, and exposure to ultraviolet light have been implicated, the connections to exfoliation syndrome remain unclear^[2]. Recent studies have implicated variants in the gene LOXL1 as a major risk factor for exfoliation syndrome and glaucoma^[2][6].

What Causes This Condition?

Exfoliation syndrome is a genetically determined systemic condition, meaning it involves the entire body but manifests primarily in the eyes^[3][5]. The main features include problems with elastin metabolism (a disturbance called elastosis) and abnormal production and breakdown of several components of the material that surrounds cells^[3].

The condition is characterized by the accumulation of an abnormal fibrillar substance that has specific staining properties. This substance accumulates on various tissues in the front segment of the eye, including the trabecular meshwork, corneal inner layer, iris tissues and blood vessels, and lens surface cells^[2].

When exfoliation syndrome progresses to exfoliation glaucoma, elevated intraocular pressure (IOP, or eye pressure) results from blockage of the trabecular meshwork by both pigment and exfoliative material trapped in the drainage spaces^[2]. As the abnormal lens material rubs against the iris, pigment is released and deposited in structures throughout the front of the eye, including the drainage angle^[2].

Signs and Symptoms

Exfoliation syndrome is often subtle and can be overlooked^[2]. The most common and obvious sign is a white and flaky material that can be seen on the border of the iris (the colored portion of the eye) or on the surface of the eye lens^[7]. The material appears as white flecks on the edge of the pupil^[2].

When the pupils are dilated during an eye examination, doctors can see a characteristic target-like pattern on the lens. This pattern is caused by scraping of the back surface of the iris against the lens surface^[2]. The white and flaky material represents the accumulated fiber or exfoliative material that is unique to this condition^[7].

Other characteristic findings include loss of the normal fringe around the pupil margin and areas where light can shine through the iris (called transillumination defects)^[2]. The white flaky deposits may peel off the outer layer of the eye lens over time^[7].

Exfoliation glaucoma often produces no noticeable symptoms in its early stages^[7]. However, in severe or advanced stages of the disease, symptoms may include sudden vision loss, severe brow ache around the eye, nausea and vomiting, and loss of side or peripheral vision^[7].

It is common for one eye to develop this condition earlier than the other eye, but both eyes are at risk for glaucoma if exfoliation material is present^[5]. The condition most often presents in an asymmetric manner^[2].

How is it Diagnosed?

A careful eye examination after pupillary dilation is essential to detect the subtle signs of exfoliation syndrome^[5]. Your doctor will perform a thorough examination of the lens to look for the characteristic white flaky material and target-like pattern^[5].

A procedure called gonioscopy, which allows the doctor to examine the drainage angle of the eye, can reveal increased pigmentation of the trabecular meshwork and possibly an accumulation of pigment along a specific structure called Schwalbe line, known as the Sampaolesi line^[2]. The corneal inner layer may also show exfoliative material appearing as white flecks, similar to what is seen in another condition called pigment dispersion syndrome^[2].

Depending on the degree of weakness in the lens support structures (zonules), the drainage angle may appear narrowed due to forward movement of the lens. The doctor may also notice lens wobbling if significant weakness of these support structures has occurred^[2].

Regular comprehensive eye examinations are the best way to detect eye conditions such as glaucoma early, so that treatment can begin before the condition develops into something more serious^[5].

Why Early Detection Matters

Exfoliation glaucoma typically presents with significant optic nerve head and visual field damage already present at the time of diagnosis, at least in one eye^[3]. As a group, patients with exfoliation glaucoma show higher pressures and faster disease progression than patients with classic primary open-angle glaucoma^[1].

Glaucoma associated with exfoliation syndrome is often associated with high intraocular pressure, which can be very difficult to control^[2]. Greater visual field loss, wider pressure variation, and more pronounced optic nerve damage can occur in this patient population compared with patients who have primary open-angle glaucoma^[2].

Additionally, studies have shown changes in the part of the optic nerve called the lamina cribrosa, suggesting a pre-existing vulnerability of the optic nerve in these patients^[2]. Sometimes eye pressure can be very high, even higher than 50 mmHg. One clue that raises suspicion for exfoliation glaucoma is if there is a big difference in the severity of the disease between the two eyes^[14].

Careful follow-up of patients with exfoliation syndrome is essential to monitor eye pressure levels and watch for early structural and functional changes that indicate transition to glaucoma^[15]. If glaucoma is not yet present, patients with exfoliation syndrome should be seen in the clinic every 6 months^[4]. For those who have developed exfoliation glaucoma, more frequent monitoring—often every 4 months—is recommended until the disease stability is understood^[4].

Treatment Options

The primary goal of exfoliation glaucoma treatment is to reduce eye pressure that is responsible for damaging the optic nerve^[7]. To provide long-term disease stability, a low mean eye pressure (less than 17 mmHg) and narrow 24-hour pressure fluctuation should be achieved^[15]. Depending on the severity of the disease, treatments may include eye drops, laser treatments, or surgery^[7].

Medications

In the early stages of exfoliation glaucoma, eye pressure control often can be achieved with medication^[4]. However, while medications can be effective in reducing eye pressure, they do not address the underlying cause of the disease^[4]. In some patients, as the condition progresses, medications alone may become insufficient^[4].

Fixed-dose combination eye drops (medications that contain more than one drug in a single bottle) may help support patient adherence to treatment^[3][15]. Prostaglandin analog therapies, which are used once daily, are convenient and can be easily administered by another person in elderly patients who are unable to give themselves eye drops^[15].

Laser Treatment

Selective laser trabeculoplasty (SLT) can be a helpful additional treatment for exfoliation glaucoma patients who require more eye pressure lowering^[4]. Although it can provide moderate pressure reduction, SLT may not be as effective for advanced disease, and its effect might not last as long in patients with exfoliation glaucoma compared to other types of glaucoma^[4].

Both argon and selective laser trabeculoplasty need to be considered during the long-term management of the disease^[3]. The actual value of pressure reduction achieved by removing exfoliation material and pigment from the trabecular meshwork should be determined, as the effect from the procedure is usually temporary^[15].

Surgical Options

When medical management and laser therapy fail to control eye pressure, surgical options are required^[4]. For mild cases of exfoliation glaucoma, minimally invasive glaucoma surgery (MIGS) is often the first-line surgical intervention^[4]. These procedures are less invasive, have a quicker recovery time, and carry a favorable safety profile^[4].

For moderate to severe exfoliation glaucoma, procedures such as gonioscopy-assisted transluminal trabeculotomy (GATT) are becoming increasingly important options. GATT offers a more robust approach by targeting the underlying problem, removing the blocked trabecular meshwork and allowing for more effective fluid drainage from the eye^[4].

Trabeculectomy and tube shunt surgeries remain the gold standards for managing advanced exfoliation glaucoma^[4]. These procedures provide significant pressure reduction but come with risks, such as infections, surgical site failure, or very low eye pressure^[4]. Various forms of surgery including deep sclerectomy, viscocanalostomy, trabecular aspiration, and cataract surgery all need to be considered during long-term disease management^[3].

Cataract extraction may result in reduction of the diffused abnormal material, and it has been reported that eye pressure is easier to control after cataract surgery^[6]. However, the risk of surgical complications during cataract surgery is high in patients with exfoliation syndrome, and surgical caution must be exercised^[6].

Connections to Overall Health

Some researchers consider exfoliation syndrome to be a systemic disease that affects the whole body and have associated it with widespread cardiovascular complications, including hypertension, stroke, heart attacks, and transient ischemic attacks^[6]. Fibrillar material similar to what is found in the eye has been identified in autopsy material from many internal organs including heart, kidney, liver, and the membranes covering the brain and spinal cord^[6].

Since exfoliation glaucoma is a disease of the elderly and is frequently associated with systemic vascular disease, consultations with other medical specialists are of great clinical importance^[3][15]. However, it is currently not recommended that all individuals with eye-related exfoliation undergo general systemic evaluations, as the mortality rate among patients with exfoliation syndrome does not appear to be increased^[6].