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Pseudoexfoliation syndrome

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Kristen Lambert
BS

Leonid Skorin Jr
OD DO MS FAAO FAOCO

Mayo Clinic Health System, Albert Lea MN, USA

 

Pseudoexfoliation syndrome (PXF) is a systemic condition that primarily affects the eyes. It is not a true exfoliation but consists of white, flaky material that is deposited on the lens capsule and other anterior eye structures. True exfoliation is extremely rare and is usually seen in glassblowers whose exposure to infrared radiation over time causes the delamination of the anterior lens capsule. There is some argument about whether pseudoexfoliation should actually be named exfoliation syndrome because true exfoliation is uncommon, and both nomenclature can be found in the literature.1,2

Pseudoexfoliation syndrome is traditionally described as affecting people of Scandinavian decent; however, it can also be found in other European ethnic groups as well as in the Middle East, Southeast Asia, India, South Africa, and South America.2 The incidence increases with age and is rarely seen in those younger than 50 years old. An incidence of one per cent in ages 52-64 and five per cent in those over 75.6 years old has been reported in the United States.3 England, Germany and France have a prevalence of 1-5 per cent.3 In older Scandinavians (over 60 years), the prevalence has been reported to be as high as 20-25 per cent.3 The condition is familial and seems to portray autosomal dominant inheritance, according to recent studies.1,3 Prevalence appears to be equal between the sexes.1,2,4 Other studies indicate a higher prevalence in women.3

Risk factors are thought to be high altitude, diet and exposure to ultraviolet light, although the aetiology is still poorly understood.2 PXF is not associated with any specific systemic disease, but pseudoexfoliation material deposits in tissues that are histologically similar to those in the anterior segment of the eye including the skin, heart, lungs, liver, kidneys, meninges and gall bladder.1 There is no evidence that PXF causes an increase in mortality.4

Although it has been extensively researched, the exact composition of the white, dandruff-like material is still unknown. The substance is a fibriller glycoprotein material and is believed to be the result of either abnormal metabolism or overproduction of glycosaminoglycans from the basement membrane of pre-equatorial lens epithelium, non-pigmented ciliary epithelium, iris pigment epithelium, corneal and trabecular endothelium, and iris stromal cells.3

Clinical signs

Diagnosis of PXF is usually based on the slitlamp finding of deposits on the lens capsule.4 The pseudoexfoliative material classically appears on the anterior lens capsule in a ‘bull’s eye’ or ‘target’ pattern (Figure 1) with a central disc, clear middle zone and granular peripheral zone often with serrated edges which is best seen with pupil dilation (Figure 2). The clear area is due to the rubbing of the posterior iris on the capsule during physiologic dilation and constriction of the pupil. This also leads to liberation of iris pigment causing iris transillumination defects and pigment deposition in the trabecular meshwork that can be seen with gonioscopy.1,3 The white, flaky material deposits on the pupillary border in 32-94 per cent of patients.3 Loss of pupillary ruff may occur leading to an inverted ruff in some cases.

OL 983 Figure 1 OL 983 Figure 2

Figure 1. ‘Bull’s eye’ appearance of pseudoexfoliative material where physiological dilation and constriction of the pupil create a clear zone on the anterior lens capsule surrounding a central disk (arrow)

Figure 2. Serrated presentation of pseudoexfoliative material on anterior lens capsule

Pupils often dilate poorly in PXF because the iris is more rigid than normal in this condition or, more likely, because of sphincter and dilator muscle degeneration.3 Posterior synechiae formation is also possible.1 The corneal endothelium may have a dusting of pseudoexfoliative material and iris pigment granules resembling Krukenberg’s spindle in pigmentary dispersion syndrome. However, in PXF, the deposits are larger and more diffuse. The liberated pigment may settle anterior to Schwalbe’s line creating a distinct Sampaolesi’s line that may be viewed with gonioscopy. The deposits first accumulate on the zonules and ciliary body where the material is actively produced. Pseudoexfoliative material may be seen on the vitreous face, posterior capsule, and the intraocular lens (IOL) after cataract extraction.3 PXF is bilateral but asymmetric in the vast majority of cases.1

Lens complications

Patients with PXF have accelerated cataract formation, particularly with nuclear sclerotic cataracts.1,3 Deposition of pseudoexfoliative material on the zonules is believed to cause proteolytic damage leading to zonular weakness and breakage, which may result in phakodonesis or spontaneous subluxation of the natural lens or IOL.2,5 It stands to reason that the more pseudoexfoliative material present, the more likely phakodonesis or pseudophakodonesis may occur, although it has been reported that the degree of zonular weakness does not seem to correlate with the amount of material visible.3,5

Patients with PXF are about 10 times more inclined to have cataract surgery complications, both intraoperatively and postoperatively (Table 1).6 Intraoperative complications include poor pupil dilation, capsular rupture, zonular dehiscence, lens displacement and vitreous loss.1,3 The risk of vitreous loss is up to 10 times higher than in eyes without PXF. Complications can be minimised by mechanically dilating pupils smaller than 6.0 mm with iris hooks especially since progressive pupil constriction may occur during surgery.4

OL 983 Table 1
Table 1. Complications associated with cataract surgery in PXF.3,5 Note: not a complete list

If capsular wrinkling is present during the initial capsulotomy, significant zonular weakening is present and capsular tension rings to stabilise the capsular bag may need to be used. Making a larger capsulorhexis can also help reduce stress on the zonules. If there is a high amount of zonular dehiscence, suturing the IOL implant or using an anterior chamber IOL should be considered.2 Postoperative complications include posterior capsular opacification, IOL and capsular bag decentration (Figure 3), capsular contraction (phimosis) (Figures 4 and 5) and transient intraocular pressure (IOP) elevation. In one study, the average time between IOL implantation and dislocation was seven years.3

OL 983 Figure 3
Figure 3. Iris capture due to IOL subluxation post-cataract extraction

OL 983 Figure 4 OL 983 Figure 5
Figure 4. Anterior capsule phimosis right eye in patient with PXF Figure 5. Anterior capsule phimosis left eye in patient with PXF

Pseudoexfoliative glaucoma

Pseudoexfoliative glaucoma (PXG) is the most common cause of secondary open-angle glaucoma in the world, accounting for 20-25 per cent of all chronic open-angle glaucoma,3,6 and 40-50 per cent of patients with PXF go on to develop PXG.2,3,6 In one study, 44 per cent of patients with PXF were diagnosed with PXG within 15 years.7 Although there is disagreement on whether PXF is more prevalent in males or females, there is little disagreement in the literature that there is equal gender prevalence in PXG.1,3 It is unknown why some patients with PXF develop PXG, but according to recent studies, the most important risk factor for predicting the conversion was initial IOP.3

In PXF, white, flaky material and pigment are deposited passively in the trabecular meshwork, but there is no glaucomatous increase in IOP. Mechanical clogging of the trabecular meshwork by pigment granules is thought to be the main cause of decreased aqueous outflow leading to a rise in IOP and subsequent damage of the nerve fibre layer in PXG. In one study, the amount of pseudoexfoliative material in the trabecular meshwork was similar in PXG and non-glaucomatous PXF eyes while the degree of pigment was much greater in eyes that were considered glaucomatous.1 Other possible mechanisms of PXG include cellular dysfunction of the trabecular meshwork or of the endothelium of Schlemm’s canal.3

Most cases of PXG are secondary open-angle glaucoma. In some instances, IOP can rise suddenly and an acute form of open-angle glaucoma with similar signs and symptoms as acute angle-closure can occur.2 Patients may experience blurred vision, red eyes, corneal oedema, and IOPs 50 mmHg or higher. Eyes with PXF are also more likely to have narrow angles that may lead to angle-closure glaucoma. This occurs because of the formation of posterior synechiae or from pupillary block caused by zonular weakness and forward displacement of the natural lens.

PXG is more difficult to manage than primary open-angle glaucoma (POAG) and has a worse prognosis. Compared to POAG, PXG usually has a poorer response to medications, more frequent need for surgical intervention, more diurnal fluctuation of IOP and worse visual field defects at the time of diagnosis. Glaucomatous changes to the optic nerve are more diffuse in PXG than in POAG where cupping is usually observed inferotemporally or superotemporally.3 The optic nerve may be especially vulnerable in PXG due to elastosis of the lamina cribrosa.2

Treatment for pseudoexfoliative glaucoma

There is no known mechanism to prevent PXF from progressing to PXG. Since IOPs can rise within a matter of months, it is important to monitor patients with PXF every four to six months to check IOP and perform yearly dilated fundus exams and visual fields. PXF patients with concomitant ocular hypertension should be treated earlier and more aggressively to delay glaucomatous damage.3

PXG is treated much like POAG. First-line therapy is pharmaceutical with prostaglandin analogs which can successfully lower IOP by increasing uveoscleral outflow. Medications that decrease aqueous production (beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists) have also been shown to be effective in lowering IOP.1 Theoretically miotics should be a first-line therapy because they can also slow progression by preventing the rubbing of the iris on the lens and decreasing the amount of iris pigment liberated while the pupil is constricted. However, miotics are not the drug of choice because posterior synechiae may develop and many patients also have nuclear sclerotic cataracts which contraindicate the use of miotics.3

Cataract extraction helps to decrease IOP and helps to prevent liberation of iris pigment because the iris rarely continues to rub along the IOL implant. Extraction is not a cure because pseudoexfoliative material still accumulates in pseudophakic eyes.4

Surgical treatment is often needed as an adjunct therapy. Argon laser trabeculoplasty (ALT) is more effective in PXG than in POAG initially, particularly because of the high pigment deposition in the trabecular meshwork. Unfortunately, the success rate of ALT in both PXG and POAG decreases to 35-55 per cent in three to six years.1 Selective laser trabeculoplasty (SLT) has similar initial and diminishing success rates as ALT. Trabeculectomy success rates also decline with time. In one study, successful IOP control (considered 21 mmHg or less) was maintained in 52 per cent of patients after four years.3 Success rates improved if cataract extraction was performed at the same time as the trabeculectomy with 2-4 mmHg lower at 12 months.3

Other surgical options include increasing aqueous outflow by bypassing the trabecular meshwork with Trabectome or iStent and decreasing aqueous production with endoscopic cyclophotocoagulation.6,8 If a patient with PXF or PXG also has a narrow angle, laser iridotomy should be considered.6

Conclusion

PXF is more common in certain ethnicities but can be found worldwide. It is important to have an understanding of the clinical and surgical implications this condition presents. Natural lens and IOL dislocation, cataract surgery complications and PXG are constant considerations for any patient with pseudoexfoliation. There is no cure but as clinicians, we must be diligent in managing this condition.

  1. Sowka J. Pseudoexfoliation syndrome and pseudoexfoliative glaucoma. Optometry 2004; 75: 4: 245-250.
  2. Minnal V, Bell NP. Exfoliation syndrome. Glaucoma Today 2013; 11: 6: 24-28.
  3. Malinovsky V, Tonekaboni K. Revisiting exfoliation syndrome. Clinical & Refractive Optometry 2003; 1: 14: 301-309.
  4. Pasquale LR. Management of exfoliation syndrome. Ophthalmology Rounds 2007; 1: 9: 1-6. SNELL Medical Communication Inc & Massachusetts Eye and Ear Infirmary, Department of Ophthalmology.
  5. Calafati J, Tam D, Ahmed I. Pseudoexfoliation syndrome in cataract surgery. Eye Net Magazine 2009; http://www.aao.org/publications/eyenet/200904/pearls.cfm (accessed December 2013).
  6. Ahmed I. The art of managing PXF glaucoma. Review Ophthalmol 2012; http://www.revophth.com/content/d/cataract/c/33327/ (accessed December 2013)
  7. Jeng S, Karger R, Hodge D, Burke J, Johnson D, Good M. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma 2007; 16: 1: 117-121.
  8. Lin S. Endoscopic cyclophotocoagulation. Brit J Ophthalmology 2002; 86: 12: 1434-1438.


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