A fibrillar, proteinaceous substance is formed in unusually high amounts within ocular tissues as a result of pseudoexfoliation syndrome, a systemic condition. It is the most prevalent cause of unilateral glaucoma and the most frequent cause of secondary glaucoma worldwide. The Framingham Eye Study found that in a U.S. population, the prevalence of pseudoexfoliation syndrome was 0.6 percent overall in people aged 52 to 64 and rose to 5 percent in people aged 75 to 85. Additionally, compared to other types of glaucoma, the resulting pseudoexfoliation glaucoma reacts poorly to medical treatment and can hasten the course of optic nerve damage. Ophthalmologists should check the eye for indications of pseudoexfoliation syndrome because it is a significant risk factor for glaucoma development and because pseudoexfoliation glaucoma is common and severe.

Pseudoexfoliation Syndrome: What Is It?

The lens, iris, ciliary epithelium, corneal endothelium, and trabecular meshwork can all develop deposits of whitish-gray protein in pseudoexfoliation syndrome, a systemic condition with mostly ocular signs. The lens epithelium, trabecular meshwork, iris, ciliary processes, conjunctiva, and periocular tissue are the material’s sources, according to pathologic analysis, despite attempts to identify it being futile. The substance, which floats in the aqueous humor and is insoluble, is filtered and then deposited in the trabecular meshwork. The trabecular endothelial cells proceed to produce the proteinaceous substance locally in the meanwhile. The trabecular gaps become clogged with all of this, which focally collapses Schlemm’s canal. IOP rises and aqueous humor outflow declines as a result.

It’s vital to understand that not everyone who has pseudoexfoliation syndrome will also have the condition. However, pseudoexfoliation syndrome dramatically increases the risk of those affected developing elevated IOP and ultimately causes pseudoexfoliation glaucoma in 15% to 30% of cases.

Etiology

Our knowledge of the etiology of PXF has substantially improved as a result of recent genetic investigations, which were first conducted in Iceland and then carried out in the United States, Germany, Italy, and South Africa. For the metabolism of elastin, the (LOXL1)  lysyl oxidase-like protein 1 gene is crucial. The creation of pseudoexfoliative material has been attributed to defects in elastin metabolism. Single nucleotide polymorphisms in the LOXL1 gene have been discovered to have a substantial correlation with the emergence of PXF and secondary glaucoma. The risk alleles, however, differ amongst populations. The high-risk genes found in the populations of Iceland and the USA were protective in a group from South Africa. No risk allele that is consistent across all populations has yet been found. Additionally, the majority of individuals in a community who possess the high-risk alleles do develop PXF, indicating that additional factors may play a role in the disease’s development.

Pseudoexfoliation Syndrome Risk Factors

Who is most susceptible to pseudoexfoliation syndrome? Before the age of 50, it is very uncommon, and as people get older, it becomes more common. Women are more likely than men to experience it. Scandinavian nations have a significant prevalence of pseudoexfoliation syndrome, which is thought to be the root cause of 50% of open-angle glaucoma cases there. On the other hand, it is comparatively uncommon among Eskimos and African Americans. However, it is also more prevalent in South Africa, South America, the Middle East, and Europe. Pseudoexfoliation syndrome most likely affects all populations, in fact. Besides age, gender, and ethnicity, genetics is also a risk factor. A LOXL1 gene variation increases the incidence of pseudoexfoliation glaucoma in some individuals.

Signs and Symptoms

On slit-lamp assessment, the symptoms of pseudoexfoliation syndrome are typically discernible. Biomicroscopy-based clinical examinations have a sensitivity and specificity of 85% and 100%, respectively.

The pupillary edge of the iris or the anterior side of the lens may have white, flaky material as a telltale sign of pseudoexfoliation. On the anterior lens capsule, the lens frequently exhibits a “three-ring sign” that comprises a core area of visible exfoliation material approximately 1 to 3 millimeters in diameter, along with a middle clear zone and a peripheral foggy ring. The edges of the core zone can be curved and are typically clearly defined. It is believed that the pseudoexfoliative material from the lens is removed from the middle clear zone by the posterior surface of the iris. Additionally, the iris pigment is lost as a result, which may cause transillumination issues.

The trabecular meshwork frequently exhibits an accumulation of pigment granules. Normally, the foggy ring around the edge of the lens is only noticeable when it is dilated. The anterior chamber depth of these individuals should be determined prior to dilatation in order to prevent the onset of acute angle-closure glaucoma. It is significant to highlight that more than 20% of patients with pseudoexfoliation syndrome have concomitant narrow angles.

Pigment deposition on the trabecular meshwork, often more pronounced inferiorly, and pigment surrounding Schwalbe’s line is both visible during gonioscopy. Additionally, the iris surface, corneal endothelium, and zonules have all been found to contain pseudoexfoliation material.

IOP often rises unilaterally in pseudoexfoliation glaucoma patients more quickly than in those with primary open-angle glaucoma (POAG). The greater IOP seen in pseudoexfoliation glaucoma might cause optic nerve injury and loss of visual field to occur more quickly. Since pseudoexfoliation glaucoma will manifest in the opposite eye in more than 40% of patients with symptoms in one eye, the contralateral eye must be thoroughly evaluated and monitored when symptoms are present in the other eye.

Patients with pseudoexfoliation syndrome and accompanying glaucoma usually experience poor pupillary response to dilation, a modest finding. This can make cataract surgery more difficult and is thought to be related to the atrophy of the iris dilator muscle. These eyes also have poor zonular attachments, which makes cataract treatment more difficult.

Prevention

There are no primary preventative methods for PXF at the moment. The difficulties of PXF can, however, be avoided by being aware of the condition. Patients with PXF and no glaucoma symptoms should have their IOP checked annually. As a result, glaucoma might be treated and prevented early on, or at the very least, the risk of developing advanced glaucoma would be decreased. Anyone having cataract surgery should be closely examined for PXF. The likelihood of surgical complications may then be reduced by taking additional precautions.

Differential Diagnoses 

Glaucoma with pigment. In pigmentary glaucoma, pigment deposition is also seen on the trabecular meshwork (TB) and anterior segment structures. Pigment dispersion syndrome, an autosomal dominant condition characterized by pigment liberation from the iris epithelium, is the root cause of pigmentary glaucoma.

The pathogenesis of this condition is similar to that of pseudoexfoliation glaucoma in that material builds up in the trabecular meshwork, causing increasing trabecular dysfunction and elevated IOP. However, pigmentary glaucoma develops early, with patients often between the ages of 20 and 40 experiencing ocular hypertension. The Krukenberg’s spindle or Zentmeyer line, also known as a vertical pigment band on the corneal endothelium, is a characteristic of pigmentary glaucoma that is frequently absent in pseudoexfoliation glaucoma. A deficiency in iris transillumination can occur in both pigmentary and pseudoexfoliation glaucoma. In contrast, the defects in pseudoexfoliation glaucoma are more patchy and closer to the pupillary edge while the defects in pigmentary glaucoma are slitlike in a radial pattern of the mid-peripheral iris. Another differentiating characteristic of pigmentary glaucoma is a propensity for the iris to have a peripheral concave form.

Open-angle glaucoma

POAG ought to be taken into account in the differential. As was already mentioned, the IOP tends to rise in POAG more gradually than it does in pseudoexfoliation glaucoma.

Amyloidosis

Amyloid material that mimics pseudoexfoliation material can accumulate in a similar pattern during amyloidosis and may even cause glaucoma. Although amyloidosis affects the kidney, liver, and spleen in addition to causing noticeable non-ocular symptoms, it is a systemic illness.

Exfoliation

True exfoliation (capsular delamination), which typically occurs in glassblowers after prolonged exposure to high heat, is also included in the differential. This condition is characterized by the peeling off of the anterior lens capsule’s capsules and subsequent thin membranes. A membrane may potentially peel off as a result of severe uveitis.

The best treatment for pseudoexfoliation glaucoma

IOP reduction is the only proven treatment for glaucoma. For PXF glaucoma, this is accurate. The goal is to stop or lessen the progression of glaucomatous optic nerve damage.

Medical treatment

When opposed to therapy for POAG, medical therapy for PXF glaucoma is more challenging.  The 24-hour IOP characteristics and strong IOP variations make it harder to reach the predetermined target pressure, even though the IOP decrease may be initially greater with a chosen agent. As a result, complementary therapy involving additional drugs or laser therapy is frequently required. These individuals’ medically untreated glaucoma necessitates earlier surgical surgery as well. 

In cases when zonular laxity is the underlying issue, medical treatment for PXF secondary angle closure differs from PACG. Instead of miotics, dilating drops (like atropine) are needed.

Surgery

Due to the more pigmented angles, laser trabeculoplasty has been said to be particularly successful in PXF glaucoma. However, the effectiveness of IOP lowering is short-lived; within 5 years, more than 50% of patients experience failure. See the section Laser Trabeculoplasty: ALT vs SLT for further information.

Patients with PXF frequently need cataract surgery because of the elevated incidence. Additionally, difficulties are more likely due to zonular weakness and insufficient pupil dilation. In these eyes, vitreous loss occurs 5–10 times more frequently. It requires slow and delicate surgery, potentially with the help of capsular staining and iris hooks. Small pupils may benefit from the hooks, which can also be inserted into the capsular bag in cases of zonular laxity. A primary cutting method could ease the strain on zonules, which are already fragile. The risk of intra-operative or late post-operative intraocular lens/bag dislocation may be decreased by inserting a capsular tension ring. To avoid anterior capsule contraction and opacification during surgery, a bigger capsulorhexis should be constructed.  These eyes are more susceptible to developing posterior capsule opacification and postoperative inflammation.

Patients with PXF glaucoma have a greater trabeculectomy complication rate than those with POAG. Success rates are comparable, though. Combining cataract and glaucoma surgery is occasionally thought of due to the rising prevalence of cataracts.

Prognosis

Does having pseudoexfoliation syndrome increase your risk of getting glaucoma? It is expected that 40 to 50 percent of people with pseudoexfoliation syndrome would eventually develop glaucoma, even if there are some patients in whom pseudoexfoliation material is visible but there are no symptoms of glaucoma. Since this syndrome has no symptoms and must be detected by an ocular examination, it is crucial that persons who have been diagnosed with it are monitored over time to check for the onset of glaucoma. Pseudoexfoliation syndrome can, in fact, occasionally be modest and overlooked. The diagnosis is made after a thorough examination by an ophthalmologist, which includes a close evaluation of the drainage angle and a dilated eye exam.

Summary

A kind of glaucoma known as pseudoexfoliative glaucoma is characterized by the buildup of abnormal material on the surface of the eye, notably on the lens and other internal structures. Pseudoexfoliation syndrome, where flaky, whitish debris builds up on various regions of the eye, is frequently linked to it.

Capsular glaucoma with pseudoexfoliation of the lens is the term used to describe pseudoexfoliation when it affects the lens. The abnormal material in this disorder has the potential to obstruct the fluid drainage passages of the eye, increasing intraocular pressure and perhaps harming the optic nerve.

Pseudoexfoliation glaucoma is often treated using a variety of methods. The main objective is to reduce intraocular pressure and stop the optic nerve from suffering additional harm. The best eye drops for pseudoexfoliation glaucoma are used to either augment or decrease the drainage of aqueous humor (the fluid inside the eye).

Depending on the patient and their unique requirements, several eye drops may be chosen for pseudoexfoliation glaucoma. Prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors are all frequently used eye drops. The patient’s intraocular pressure, general health, and any coexisting medical disorders are frequently taken into account while choosing eye drops.

In addition to eye drops, trabeculectomy or the installation of glaucoma drainage devices are two other treatments for pseudoexfoliation glaucoma. Laser operations, such as laser trabeculoplasty, are also a possibility. These treatments are intended to improve fluid drainage from the eye and lower intraocular pressure.

Regular follow-up care with an ophthalmologist or glaucoma specialist is crucial for those with pseudoexfoliation glaucoma. In order to maintain eyesight and stop future damage to the optic nerve, they will evaluate the disease’s progression, alter medication as necessary, and provide continuing management.

FAQ’s

How serious is pseudoexfoliation?

Pseudoexfoliation glaucoma (PEG), a prevalent cause of blindness in the entire world, is more severe and progresses more quickly than primary OAG (POAG).

Pseudoexfoliation: is it treatable?

Although pseudoexfoliation syndrome cannot be prevented or treated, it can be successfully managed when your doctor and you work together.

Does pseudoexfoliation run in families?

The lysyl oxidase-like 1 gene (LOXL1) has recently been closely linked to the condition XFS, which has a strong familial relationship. Due to its role in the manufacture and upkeep of elastic fibers, this gene provides a compelling biological case for its involvement in this illness.