Nixon Phua Cher Yang1, Priyal Taribagil2
1– Foundation Doctor, Imperial College Healthcare NHS Trust
2 – Academic Foundation Doctor, Royal Free Foundation Trust
Abstract
Pseudoexfoliation Syndrome (PEX) is a systemic disease characterised by the deposition of extracellular fibrillary material in the anterior segment of the eye. It is often identified incidentally on slit lamp examination because patients are typically asymptomatic during initial stages. It is associated with raised intraocular pressure and development of secondary glaucoma. Due to the increased disposition of PEG, patients with PEG should be routinely monitored so that early interventions could be introduced to slow down the progression of glaucomatous changes.
Introduction
Pseudoexfoliation Syndrome (PEX) is a systemic disease characterised by the deposition of extracellular fibrillary material in the eye and other body tissues such as heart and lungs. The accumulation of these dandruff-like material in the anterior segment of the eye is associated with raised intraocular pressure and development of glaucoma. Study has shown that up to 44% of PEX patients ultimately develop pseudoexfoliation glaucoma (PEG), rendering it one of most common causes of secondary open-angle glaucoma (1). Unlike its ocular manifestations, the morbidity, and causal effects of the disease in other body organs are yet to be fully elucidated.
Pathophysiology
PEX results from the abnormal deposition of fibrils formed from the aggregation of fibrillin molecules and cross-linkage of microfibrils. These aggregates are formed in various epithelial and endothelial cells in the anterior segment in a process driven by oxidative stress. They are then released extracellularly and deposit in structures such as the anterior lens and pupillary margin. The deposition could then lead to obstruction of trabecular meshwork, reduction in aqueous flow, increase in intraocular pressure and subsequent development of glaucoma. Besides that, build-up of the fibrillary material in the lens zonules could also result in zonular weakness, lens instability and dehiscence (2).
Risk factors
The main risk factors associated with PEX include older age, Scandinavian population and female gender. Like primary open-angle glaucoma, the incidence increases with age. A study done in Reykjavik showed that incidence increase from 6.5% in participants aged 50 to 59 years old to 10.6% in participants aged 70-79 years old (3). PEX is also noted to be more common in Scandinavian countries, with prevalence ranging between 22.4% in Finland to 30% in Iceland (4, 5). In comparison, a prevalence of mere 3.5% is observed in Saudi Arabia (6). Besides, higher prevalence is also seen in women compared to men. For instance, a study done in Croatia showed PEX to be almost twice more prevalent in females compared to males (7).
Clinical features and assessment
PEX is often found incidentally during slit lamp examination because most of the patients are asymptomatic. However, some patients might present with loss in peripheral vision as a result of secondary glaucoma. It is usually diagnosed clinically with slit lamp assessment and gonioscopy.
Slit lamp assessment
Despite being a systemic disease, it is not uncommon to only note PEX findings unilaterally rather than bilaterally. Bilateral involvement is more evident in older population (8).
The most classic finding involves visualisation of white dandruff-like material of PEX in the anterior lens capsule. It is observed in three different zones, in the form of a clear intermediate zone between a central disc and peripheral circle of PEX material. The intermediate zone is clear because the PEX material is cleared off the lens following iris excursion rubbing. The peripheral ring is more subtle compared to the central zone and is often missed without pharmacological dilatation. Moreover, cataract formation may also be noted, especially nuclear sclerotic and subcapsular cataracts.
Not only that, flaky PEX material can also deposit in the endothelium of cornea. The distribution of the PEX material could be either in the pattern of diffuse dispersion or spindle configuration (9).
When looking at the iris, PEX pigment can sometimes be seen at both the anterior and posterior surfaces. The pupillary margin frequently shows transillumination defects as a result of pupillary ruff atrophy. This is sometimes described as the “moth eaten” pupil margin. Pupil dilation is also often poor.
Gonioscopy
Gonioscopy often demonstrates an open anterior chamber angle. However, acute angle closure has also been reported previously and is believed to secondary to increased iridolenticular adhesions caused by deposition of PEX material (10). A Sampaolesi line, which refers to accumulation of brown pigment deposit at or anterior to Schwalbe line, is also seen. However, it is worth noting that Sampaolesi line is not pathognomonic or exclusive to PEX because it is also observed in pigment dispersion syndrome.
| Structures | Findings |
| Anterior lens | – White dandruff-like material in central zone and peripheral ring, with a clear intermediate zone in between – Nuclear sclerotic and subcapsular cataracts |
| Cornea | – Deposition at corneal endothelium, the pattern of distribution could be either diffuse dispersion or spindle configuration |
| Iris | – PEX material on both anterior and posterior surfaces – Transillumination defects in pupillary margin |
| Anterior Chamber angle | – Usually open anterior chamber seen during gonioscopy – Sampaolesi line |
Other assessments
Besides slit lamp examination and gonioscopy, baseline intraocular pressure should also be measured with tonometry due to the increased risk of developing secondary glaucoma. Visual field analysis is also a useful baseline assessment because it could serve to monitor the progression if a patient develops glaucoma subsequently. Optical coherence tomography (OCT) should be performed to look for glaucomatous changes such as peripapillary retinal nerve fibre layer.
Management
There is currently no curative treatment available to reverse the changes caused by the PEX. Current management focuses on early detection and timely treatment of glaucoma to slow down the progression.
The medical management of PEX glaucoma is similar to that of primary open angle glaucoma (POAG). Topical medications that have been used to help lower the intraocular pressure (IOP) include beta-blocker, prostaglandin analogue and carbonic anhydrase. These IOP lowering agents are sometimes used in combination. Pilocarpine is generally not recommended due to its risks of causing pupillary block and posterior synechiae.
PEX glaucoma has a higher tendency to be resistant to medical treatment, and hence often requires early surgical intervention. Selective laser trabeculoplasty (SLT) is often offered as a first line therapy due to its less invasive nature. SLT is particularly effective because the increased pigmentation of trabecular meshwork is associated with a higher level if argon laser energy absorption (9). Other surgical interventions are typically offered include trabeculectomy and insertion of glaucoma drainage device.
Conclusion
PEX is a systemic condition with mainly ocular manifestations. Patients suspected of PEX will require careful slit lamp examination and regular screening for development of glaucoma. PEG should be differentiated from POAG because it has a higher rate of progression and might benefit from early surgical interventions.
Take-Home Messages
1. PEX is a systemic disease characterised by the deposition of extracellular fibrillary material in the anterior segment of the eye.
2. It is often identified incidentally on slit lamp examination because patients are typically asymptomatic during initial stages. Classic signs include deposition of dandruff-like material in anterior lens capsule and corneal endothelium as well as transillumination defect in pupillary margin.
3. PEX is associated with raised intraocular pressure and development of secondary glaucoma. Patients suspected of PEX should be monitored routinely for early glaucomatous changes.
4. Treatment of PEG is similar to that of POAG, which involves usage of medical IOP lower agents and surgical interventions such as SLT and trabeculectomy.
References
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