Pseudoexfoliation Syndrome

Pseudoexfoliation syndrome (exfoliation syndrome) is the most common cause of secondary open-angle glaucoma (OAG). It is characterized by the extracellular deposition of distinctive fibrillar material in the anterior segment of the eye. On histologic examination, this material has been found in and on the lens epithelium and capsule, pupillary margin, ciliary epithelium, iris pigment epithelium, iris stroma, iris blood vessels, and subconjunctival tissue. The material has also been identified in other parts of the body, including the skin, lungs, heart, and liver. Mutations in a single gene, LOXL1, are present in nearly all cases of pseudoexfoliation syndrome and pseudoexfoliation glaucoma; however, these disease-associated mutations are also common in populations without pseudoexfoliation syndrome, and other genes have also been implicated in genome-wide association studies, suggesting a multifactorial etiology for this disease. The exact relationship between genetic and environmental factors in pseudoexfoliation syndrome remains unclear.

Pseudoexfoliation syndrome is typically asymmetric and often presents unilaterally, although the uninvolved eye may manifest signs of the disease at a later time. This syndrome is strongly age related: it is rarely seen in persons younger than 50 years and occurs most commonly in individuals older than 70 years.

The classic characteristic of pseudoexfoliation syndrome is the deposition of fibrillar deposits in a “bull’s-eye” pattern on the anterior lens capsule, which is best viewed after pupillary dilation. This pattern is presumably caused by iris movement that scrapes the pseudoexfoliative material from the lens, causing a clear intermediate area in between a central and a peripheral zone of the material (Fig 1-8). Clinically, this fibrillar extracellular material can be seen on the pupillary margin, zonular fibers of the lens, ciliary processes, inferior anterior chamber angle, corneal endothelium, and anterior vitreous (Figs 8-2, 8-3).

Individuals with pseudoexfoliation syndrome may also have peripupillary atrophy with transillumination defects. In these patients, the pupil often dilates poorly, likely because of infiltration of fibrillar material into the iris stroma. Phacodonesis results from the weak zonular fibers. Thus, great care must be taken during cataract surgery to reduce the risk of zonular dehiscence, vitreous loss, lens dislocation, and other complications (see also BCSC Section 11, Lens and Cataract). Iris angiography has shown abnormalities of the iris vessels with leakage of fluorescein.

Figure 8-1 Pseudoexfoliation syndrome. Pseudoexfoliative material deposited on the anterior lens capsule in a classic “bull’s-eye” pattern in a dilated eye.

(Courtesy of Wallace L.M. Alward, MD. From the Iowa Glaucoma Curriculum [curriculum.iowaglaucoma.org]. © The University of Iowa.)

Figure 8-2 Pseudoexfoliative material deposited on the pupillary margin and anterior lens capsule in an undilated eye.

(Courtesy of Wallace L.M. Alward, MD. From the Iowa Glaucoma Curriculum [curriculum.iowaglaucoma.org] . © The University of Iowa.)

Figure 8-3 Goniophotograph of the anterior chamber angle in an eye with pseudoexfoliation syndrome. Note the Sampaolesi line (black arrows). White arrows indicate the anterior border of the pigmented trabecular meshwork.

(Courtesy of Angelo P. Tanna, MD.)

On gonioscopy, the trabecular meshwork is typically heavily pigmented, sometimes in a variegated fashion. Pigment deposition anterior to the Schwalbe line is commonly seen and referred to as the Sampaolesi line (see Fig 3-8). Anterior migration of the lens caused by zonular laxity may lead to secondary angle closure.

The intraocular pressure (IOP) elevation associated with pseudoexfoliation syndrome is likely attributable to deposits of fibrillar material in the conventional and uveoscleral outflow pathways that impede the outflow of aqueous humor. In addition, because elastin is an important component of the lamina cribrosa, pseudoexfoliation syndrome may increase the susceptibility of the optic nerve to injury. This increased susceptibility may, in turn, contribute to the increased risk of development and progression of glaucoma in these patients, as was found in the Early Manifest Glaucoma Trial (see Clinical Trial 7-4 at the end of Chapter 7).

Individuals with pseudoexfoliation syndrome with elevated IOP that results in optic nerve damage or visual field loss are described as having pseudoexfoliation glaucoma. Pseudoexfoliation syndrome is associated with OAG in all populations, but the prevalence varies considerably. In Scandinavian countries, pseudoexfoliation syndrome accounts for more than 50% of cases of OAG. The risk of progression to glaucoma also varies widely and can be as high as 40% of patients in a 10-year period. Patients with pseudoexfoliation syndrome often have higher IOP, with greater diurnal IOP fluctuations, than do patients with primary open-angle glaucoma (POAG). The overall prognosis for glaucoma is worse for patients with pseudoexfoliation glaucoma than for those with POAG. Laser trabeculoplasty can be very effective, but the duration of the response may be shorter in pseudoexfoliation glaucoma than in POAG.

• Aboobakar IF, Johnson WM, Stamer WD, Hauser MA, Allingham RR. Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology. Exp Eye Res. 2017;154:88–103.

• Thorleifsson G, Magnusson KP, Sulem P, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397–1400.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.