Pseudoexfoliation Syndrome (Pseudoexfoliation Glaucoma)

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Pseudoexfoliation Syndrome (Pseudoexfoliation Glaucoma)

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In 1917, a Finnish ophthalmologist named Lindberg first described pseudoexfoliation syndrome. This entity is characterized by flakes of granular material at the pupillary margin of the iris and throughout the inner surface of the anterior chamber. It is also associated with secondary open-angle glaucoma, known as pseudoexfoliation glaucoma, which is the most common identifiable form of secondary open-angle glaucoma worldwide. Dvorak-Thebold suggested the term pseudoexfoliation to differentiate it from true exfoliation or lamellar delamination of the lens capsule found in glassblowers. True exfoliation syndrome is due to heat or infrared-related changes in the anterior lens capsule.

Pseudoexfoliation syndrome is a common ocular manifestation of a systemic disease, known to cause disease primarily in the eye. Exact etiology of this condition remains unknown.

Pseudoexfoliation material is associated with abnormalities of the basement membrane in epithelial cells and has a wide distribution throughout the body. Pseudoexfoliative material has been found in the walls of the vortex veins and the central retinal artery. Extraocular tissues involved include lung, skin, liver, heart, kidney, gallbladder, blood vessels, extraocular muscle, connective tissue in the orbit, and meninges. In the anterior segment of the eye, it is characterized by deposition of pseudoexfoliative amyloidlike material on the anterior lens capsule, ciliary body, zonules, pupillary margin of the iris, corneal endothelium, anterior vitreous, and trabecular meshwork.

Some investigators believe that the iris pigment epithelium, the ciliary epithelium, and the peripheral anterior lens epithelium produce this pseudoexfoliative amyloidlike material, which moves into the aqueous humor and is carried to the trabecular meshwork, following the normal flow. Obstruction of the trabecular meshwork by this fibrillar material and pigment associated with degenerative changes in the Schlemm canal and the juxtacanalicular area causes elevation of the intraocular pressure (IOP) with associated glaucoma.

Zenkel et al have studied genes differentially expressed in anterior segment tissues and have postulated that pseudoexfoliation syndrome is a stress-induced elastic microfibrillopathy.^[1]

United States

Roth and Epstein reported that pseudoexfoliation glaucoma was present in 12% of patients with glaucoma.^[2]Kozart and Yanoff reported that glaucoma was present in 7% of 100 consecutive patients with pseudoexfoliation syndrome in Philadelphia.^[3]In the Framingham study, prevalence of pseudoexfoliation syndrome was 1.8%. In a prospective study, Cashwell and Shields found that the prevalence of pseudoexfoliation syndrome in the southeastern United States was 1.6% of the total population and in 6% of an open-angle glaucoma subpopulation.^[4]Prevalence of pseudoexfoliation syndrome in the glaucoma population of south Louisiana was found to be 2.7% in white patients and 0.4% in African American patients. Karger et al determined that the incidence of newly diagnosed pseudoexfoliation syndrome in residents of Olmsted County, Minnesota, was 25.9 cases per 100,000 population.^[5]

Because of the increased mean age of populations, pseudoexfoliation syndrome may become more prevalent in the future.

International

Prevalence of pseudoexfoliation syndrome in Europe was found to be 4.7% in England, 6.3% in Norway, 4% in Germany, 1.1% in Greece, and 5.5% in France.

Bartholomew reported an 8.2% prevalence of pseudoexfoliation syndrome in the Bantu tribes of South Africa.^[6]The prevalence in a Japanese population was 3.4%, 3.5% in Saudi Arabia,^[7]and 3.73% in a South Indian study.^[8]Hospital-based studies showed a prevalence of 6.45% in Pakistan and 7.4% in India. A prevalence rate of 0.4% was identified in China and Iran.^[9]

According to the Early Manifest Glaucoma Trial, pseudoexfoliation increases the risk of progression of early glaucoma over two-fold.^[10]

In a retrospective study, Shrum et al found no association between ocular pseudoexfoliation and cardiovascular or cerebrovascular mortality.^[11]Ekström and Kilander studied the association of pseudoexfoliation and Alzheimer disease and did not find an increased risk.^[12]

Serum levels of uric acid, alanine aminotransferase, and hemoglobin and red blood cell counts are similar in subjects with and without pseudoexfoliation.^[13]However, other authors have found that pseudoexfoliation is linked with Alzheimer disease, senile dementia, cerebral atrophy, chronic cerebral ischemia, stroke, transient ischemic attacks, heart disease, and hearing loss.^[14]Vessani et al found that homocysteine levels were higher among patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma compared with controls.^[15]Roedl et al reported increased homocysteine concentrations in tear fluid and plasma of patients with pseudoexfoliation glaucoma.^[16]Elevated plasma homocysteine levels have been described as a risk factor for cardiovascular disease.

Erectile dysfunction may be associated owing to accumulation in vessel walls.^[17]

Although it occurs in virtually every area of the world, a considerable racial variation exists in the incidence of pseudoexfoliation glaucoma.

In Scandinavian countries, more than 50% of cases of open-angle glaucoma are caused by pseudoexfoliation syndrome.

Pseudoexfoliation syndrome is relatively rare among African Americans and Eskimos. It was not observed at all in the Inuit who live throughout the Canadian Arctic.

Prevalence is high in the Sami people who are indigenous of northern Europe.

Among the Bantu tribes of South Africa, exfoliation was found in 19% of patients in a glaucoma clinic.

There is a high prevalence of pseudoexfoliation syndrome in Arabic populations. In Saudi Arabia, Summanen and Tonjum reported a prevalence of pseudoexfoliation syndrome of 13%.^[18]It has been found to be the cause of half the cases of glaucoma in Oman.^[19]

Prevalence of pseudoexfoliation syndrome in Spanish Americans in New Mexico was estimated to be 3-6%.

Pseudoexfoliation syndrome is more common in females than in males. In a series by Kozart and Yanoff, pseudoexfoliation syndrome was 3 times more common in women than in men.^[3]

Pseudoexfoliation syndrome is rarely seen before age 50 years, and its incidence increases steadily with age.

In Norway, Aasved reported that the prevalence of pseudoexfoliation was 0.4% in individuals aged 50-59 years and 7.9% in individuals aged 80-89 years.^[20]The reported mean age of pseudoexfoliation syndrome ranges from 69-75 years.

Jonasson et al reported a 10% annual increase for both open-angle glaucoma and pseudoexfoliation in persons aged 50 years and older in Iceland.^[21]

Intraocular pressure increases slightly with age in patients with pseudoexfoliation.^[22]

Most investigators agree that the prognosis for pseudoexfoliation glaucoma is worse than that for primary open-angle glaucoma because of higher IOP levels, rapid progression, and more severe optic nerve damage and visual field defects.

Brinchmann-Hansen et al reported that the response to pilocarpine treatment was less effective in controlling the IOP in patients with pseudoexfoliation glaucoma than in patients with open-angle glaucoma.

Pseudoexfoliation glaucoma patients are more likely to require laser trabeculoplasty or filtering procedures.

For excellent patient education resources, visit eMedicineHealth’s Eye and Vision Center. Also, see eMedicineHealth’s patient education articles Glaucoma Overview, Glaucoma Medications, and Glaucoma FAQs.

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Mauricio E Pons, MD Associate Physician, California Retina Associates

Mauricio E Pons, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Society of Retina Specialists