George L. Spaeth

BASICS

DESCRIPTION

• A systemic disorder characterized by the deposition of a fibrillar material on the lens, ciliary epithelium, zonules, iris, and corneal endothelium, which may be associated with the development of open- or closed-angle glaucoma

• In the U.S., approximately 40% of patients with pseudoexfoliation syndrome (PXS) develop pseudoexfoliation glaucoma (PXG).

• Differentiated from true exfoliation (capsular delamination seen in individuals exposed to infrared radiation)

EPIDEMIOLOGY

Incidence

• Varies depending on country, ethnicity, and age

• In the U.S., the incidence of PXS has been estimated to be 25.9 per 100,000, but varies by age (1)[C]:

– 40–49 years old: 2.8 per 100,000

– ≥80 years old: 205.7 per 100,000

• In the U.S., the incidence of PXG is 9.9 per 100,000, but also varies by age (1)[C]:

– 40–49 years old: 0.6 per 100,000

– ≥80 years old: 114.3 per 100,000

Prevalence

• Varies depending on location and ethnicity

• In the Framingham Eye Study, the rate of PXS was 0.6% for ages 52–64 years and 5.0% for ages 75–85 years.

• In some Scandinavian countries, PXG may account for more than 50% of open-angle glaucoma.

RISK FACTORS

• Age (more common >60 years)

• Female

• Scandinavian descent

• Family history

Genetics

• Strong familial association

• Multiple modes of inheritance (including autosomal dominant, autosomal recessive, X-linked, and maternal inheritance patterns) have been described.

• Some studies suggest that polymorphisms in the lysyl oxidase-like 1 (LOL1) gene (which is involved in the synthesis and maintenance of elastic fibers) is associated with pseudoexfoliation (2)[B].

• Polymorphisms in the clusterin gene may be a risk factor for pseudoexfoliation.

• Role of genetic testing is not clear.

GENERAL PREVENTION

No known modes of prevention

PATHOPHYSIOLOGY

• Several mechanisms of pathogenesis have been proposed:

– Elastic microfibril hypothesis: pseudoexfoliation material accumulates due to excessive synthesis of elastin fibrils.

– Pseudoexfoliation material may be composed of basement membrane proteoglycans and may accumulate due to abnormal metabolism of glycosaminoglycans in the iris.

– Overexpression of transforming growth factor β1 and an imbalance between matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases probably contribute to the pathogenesis.

• Glaucoma may be the result of accumulation of the fibrillar material in the juxtacanalicular tissue.

• Accumulation of the pseudoexfoliation material in Schlemm’s canal may lead to narrowing or collapse of this structure, also contributing to elevated intraocular pressure (IOP).

ETIOLOGY

• The exact etiology has not been elucidated.

• See Pathophysiology section for current hypotheses.

COMMONLY ASSOCIATED CONDITIONS

• Cataract

• Open or closed angle glaucoma

• Hyperhomocysteinemia

• Cardiovascular disease

• Sensorineural hearing loss

DIAGNOSIS

HISTORY

Generally asymptomatic

PHYSICAL EXAM

• Usually bilateral but frequently asymmetric

• Flakes of pseudoexfoliation material and pigment on the corneal endothelium

• Pseudoexfoliation material is seen on the anterior lens capsule in a characteristic pattern: central plaque of pseudoexfoliation material surrounded by a clear zone surrounded by a peripheral zone of pseudoexfoliation material.

• Nuclear opacities

• Pseudoexfoliation material deposits on and weakens the lens zonules, leading to phacodonesis and lens subluxation.

• Pseudoexfoliation flakes on the pupillary margin.

• Moth-eaten transillumination defects near the pupillary margin

• Iridodonesis

• Loss of pupillary ruff

• Poor mydriasis

• Increased pigmentation of the trabecular meshwork

• Sampaolesi’s line (undulating line of pigment anterior to Schwalbe’s line)

• Zonular laxity may lead to a closed angle and shallow anterior chamber depth.

• Glaucomatous optic cupping may be present

• Elevated IOP

• Mild anterior chamber flare

• On fluorescein angiography, iris vessels often leak.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Consider checking plasma homocysteine levels (hyperhomocysteinemia has been detected in 27.1% of patients with PXG) (3)[B].

Imaging

Initial approach

• Optic nerve photos

• Optic nerve imaging (confocal scanning laser ophthalmoscopy, scanning laser polarimetry, or optical coherence tomography)

Follow-up & special considerations

Repeat optic disc photos or imaging every 1–2 years.

Diagnostic Procedures/Other

• Visual fields should be obtained every 1–2 years (or more frequently if indicated by rate of glaucomatous progression).

• A-scan or IOLMaster axial length measurements and corneal curvature measurements for those undergoing cataract surgery.

• Pachymetry to assess central corneal thickness

Pathological Findings

• Eosinophilic pseudoexfoliation material is found on the anterior lens capsule, zonules, anterior and posterior surfaces of the iris, ciliary body epithelium, corneal endothelium, and incorporated into the trabecular meshwork.

• Elastin and tropoelastin are present by immunoelectron microscopy.

• Pseudoexfoliation material has been found in other ocular (conjunctiva, posterior ciliary vessels), periocular (eyelid skin, extraocular muscles, orbital septa) and extraocular (heart, lungs, liver, kidney, gallbladder, and cerebral meninges) sites (4)[B].

DIFFERENTIAL DIAGNOSIS

• True exfoliation (see Description)

• Primary amyloidosis

• Pigmentary dispersion syndrome/glaucoma

• Uveitic glaucoma

• Chronic angle-closure glaucoma

TREATMENT

MEDICATION

First Line

• Observation may be appropriate, if there are no signs of ocular hypertension or glaucoma.

• When ocular hypertension is present, close observation is warranted. As the course of PXS from normal IOP to ocular hypertension to glaucoma can be rapid, initiation of IOP-lowering treatment may be indicated.

• When signs of glaucoma are present, treatment (medications, laser, or surgery) should be initiated. Medications include the following:

– Topical prostaglandin analogues (e.g., travoprost, latanoprost, bimatoprost)

– Topical beta-blockers (e.g., timolol, betaxolol)

– Topical alpha₂-agonists (e.g., brimonidine)

– Topical carbonic anhydrase inhibitors (e.g., dorzolamide, brinzolamide)

– Fixed combination meds (e.g., dorzolamide/timolol, timolol/brimonidine)

Second Line

Oral carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide)

ADDITIONAL TREATMENT

Issues for Referral

• Consider referral to an experienced anterior segment surgeon for cataract extraction if zonular laxity is present.

• Consider referral to a glaucoma specialist when indicated.

SURGERY/OTHER PROCEDURES

• Laser trabeculoplasty can be highly effective, but the duration of effectiveness may be short compared with primary open angle glaucoma (POAG).

• Cataract extraction when lenticular opacities are visually significant (be prepared to use iris expansion techniques due to poor mydriasis and consider use of a capsular tension ring; extracapsular cataract extraction is indicated in some cases). NOTE: Pseudoexfoliation does not resolve following cataract extraction (5)[B].

• Trabecular aspiration has been described but has not been well studied.

• Trabeculectomy with mitomycin-C

• Tube shunt

• Cyclophotocoagulation may be considered when other medical and surgical treatments fail.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• Patients with PXS should be seen for a full exam annually to monitor for signs of glaucoma and/or lens subluxation.

• Patients with PXG should be seen every 3–12 months depending on disease severity.

DIET

Consider folate and vitamin B₁₂ supplementation if hyperhomocysteinemia is present.

PROGNOSIS

• Variable

• Greater diurnal IOP variation in PXG compared with POAG

• PXG is often more difficult to treat than POAG.

• When PXG progresses, it often progresses more rapidly than POAG.

COMPLICATIONS

• Lens subluxation

• Glaucomatous visual field loss

• Corneal decompensation

Stay updated, free articles. Join our Telegram channel

Join