Pseudoexfoliation syndrome

Pseudoexfoliation syndrome is a systemic condition characterized by the production and progressive accumulation of a fibrillar material in tissues throughout the anterior segment and in the connective tissue of various visceral organs (eg, lung, liver, kidney, and gallbladder) (Fig 7-8). These deposits help differentiate pseudoexfoliation syndrome from true exfoliation, in which infrared radiation induces splitting of the lens capsule. Pseudoexfoliation syndrome is usually identified in individuals older than 50 years.

Recent data suggest that the pathogenesis of pseudoexfoliation syndrome is a combination of excessive production and abnormal aggregation of elastic microfibril and extracellular matrix components (protein sink), as well as abnormal biomechanical properties of the elastic components of the trabecular meshwork and lamina cribrosa. Polymorphisms in the lysyl oxidase–like 1 gene, LOXL1, on chromosome 15 (15q24) are markers for pseudoexfoliation syndrome. Lysyl oxidase is a pivotal enzyme in extracellular matrix formation, catalyzing covalent crosslinking of collagen and elastin.

Pseudoexfoliative material is most apparent on the surface of the anterior segment structures, where it exhibits a positive periodic acid–Schiff reaction (PAS stain); presents as delicate, feathery or brushlike fibrils arranged perpendicular to the surfaces of the intraocular structures; and is easiest to identify on the anterior lens capsule (Fig 7-9A). Pseudoexfoliative material also accumulates in the trabecular meshwork and the wall of Schlemm canal, leading to increased intraocular pressure and secondary glaucoma. Associated degenerative changes in the iris pigment epithelium manifest histologically as a “sawtooth” configuration (Fig 7-9B). These degenerative changes lead to pigment aggregation in the anterior chamber angle. See also BCSC Section 10, Glaucoma, and Section 11, Lens and Cataract.

Figure 7-7 Iridocorneal endothelial (ICE) syndrome. A, Iris nevus syndrome. The normal anterior iris architecture is effaced by a membrane growing on the anterior iris surface (asterisk). The membrane pinches off islands of normal iris stroma, resulting in a nodular, nevus-like appearance (arrowheads).B, Essential iris atrophy. Atrophic holes in the iris and a narrow anterior chamber, consistent with peripheral anterior synechiae formation. C, A membrane composed of spindle cells lines the posterior surface of the cornea and the anterior surface of the atrophic iris (arrows). Metaplastic endothelial cells deposit on the iris surface a thin basement membrane that exhibits positive periodic acid–Schiff staining and is analogous to Descemet membrane. D, Descemet membrane lines the anterior surface of the iris (arrows). The iris is apposed to the cornea (peripheral anterior synechiae; asterisk).

(Part A courtesy of Paul A. Sidoti, MD; parts B and C courtesy of Tatyana Milman, MD.)

• Vazquez LE, Lee RK. Genomic and proteomic pathophysiology of pseudoexfoliation glaucoma. Int Ophthalmol Clin. 2014;54(4):1–13.

Phacolytic glaucoma

In phacolytic glaucoma, denatured lens protein leaks from a hypermature cataract through an intact but permeable lens capsule. The trabecular meshwork becomes occluded by the lens protein and by histiocytes that are engorged with phagocytosed proteinaceous, eosinophilic lens material (Fig 7-10).

Trauma

As detailed in the following discussion, blunt trauma may result in different types of secondary glaucoma.

Figure 7-8 Gross photograph shows white fibrillar deposits on the lens zonular fibers (arrows) in pseudoexfoliation syndrome.

(Courtesy of Hans E. Grossniklaus, MD.)

Figure 7-9 Pseudoexfoliation syndrome. A, Abnormal material appears on the anterior lens capsule like iron filings on the edge of a magnet (arrows).B, The iris pigment epithelium demonstrates a “sawtooth” configuration, consistent with pseudoexfoliation.

(Part B courtesy of Tatyana Milman, MD.)

Figure 7-10 Phacolytic glaucoma. A, Photomicrograph of histiocytes filled with degenerated lens cortical material in the angle. B, Higher magnification of the same image.

(Courtesy of Michele M. Bloomer, MD.)

Hyphema (Fig 7-11), defined as blood in the anterior chamber, may lead to increased intraocular pressure, peripheral anterior synechiae, hemosiderosis bulbi, and, potentially, vision loss.

Following an intraocular hemorrhage, blood breakdown products may accumulate in the trabecular meshwork. The rigidity and spherical shape of hemolyzed erythrocytes (ghost cells) make it difficult for them to escape through the trabecular meshwork. The ghost cells obstruct the meshwork and block aqueous outflow, leading to ghost cell glaucoma (Fig 7-12), one type of secondary open-angle glaucoma. Ghost cell glaucoma often follows a vitreous hemorrhage, in which blood cells may be retained for prolonged periods, allowing the hemoglobin in erythrocytes to denature.

Figure 7-11 Erythrocytes in the anterior chamber (hyphema) posterior to the cornea (asterisk).

(Courtesy of Steffen Heegaard, MD.)

Figure 7-12 Aqueous aspirate demonstrates numerous ghost cells. The degenerating hemoglobin is present as small globules known as Heinz bodies (arrows) within the red blood cells.

(Courtesy of Nasreen A. Syed, MD.)

Figure 7-13 Hemolytic glaucoma. The anterior chamber angle contains histiocytes with erythrocyte debris and rust-colored intracytoplasmic hemosiderin (arrows). Hemosiderin is also observed within the trabecular meshwork endothelium (arrowhead).

(Courtesy of Michele M. Bloomer, MD.)

In hemolytic glaucoma, another type of secondary open-angle glaucoma, histiocytes in the anterior chamber phagocytose erythrocytes and their breakdown products, and these hemoglobin-laden and hemosiderin-laden histiocytes block the trabecular outflow channels (Fig 7-13). The histiocytes may be a sign of trabecular obstruction rather than the actual cause of an obstruction.

In other cases of secondary open-angle glaucoma associated with chronic intraocular hemorrhage, histologic examinations have revealed hemosiderin within the trabeculocytes and within many ocular epithelial structures (see Fig 7-13). The hemosiderin likely releases intracellular iron, which results in intracellular toxicity, probably due to oxidative damage. This is the basis of intraocular dysfunction, including glaucoma, in both siderosis bulbi and hemosiderosis bulbi. The Prussian blue reaction can demonstrate iron deposition in hemosiderosis bulbi.

Blunt injury to the globe may be associated with angle recession, cyclodialysis, and iridodialysis. Progressive degenerative changes in the trabecular meshwork can contribute to the development of glaucoma after injury. See the section Pathologically Apparent Sequelae of Ocular Trauma in Chapter 4 for further discussion, including images.

Pigment dispersion associations

Pigment dispersion (of melanosomes) may be associated with a variety of other conditions in which pigment epithelium or uveal melanocytes are injured, such as uveitis and uveal melanoma. These conditions are characterized by the presence of pigment within the trabecular meshwork as well as in histiocytes littering the anterior chamber angle (Fig 7-14).

Figure 7-14 Melanomalytic glaucoma. The trabecular meshwork (between arrows) is obstructed by histiocytes that have ingested pigment from a necrotic intraocular melanoma.

Figure 7-15 Pigment dispersion syndrome. A, Gross photograph demonstrating circumferential transillumination defects in the iris. B, Melanin is present on the anterior surface of the lens. C, Note the focal loss of iris pigment epithelium (arrow). Chafing of the zonular fibers against the epithelium may release the pigment that is dispersed in this condition. D, Pigment accumulation in the trabecular meshwork.

Pigment dispersion syndrome can lead to a secondary open-angle glaucoma that is characterized by transillumination defects in the midperipheral iris in addition to pigment in the trabecular meshwork, the corneal endothelium (Krukenberg spindle), and other anterior segment structures, such as the lens capsule (Fig 7-15). The dispersed pigment is presumed to result from rubbing of the lens zonular fibers against the iris pigment epithelium. See also BCSC Section 10, Glaucoma.

Figure 7-16 Photomicrograph shows melanoma cells filling the anterior chamber angle and obstructing the trabecular meshwork. The iris pigment epithelium is present in the lower right corner of the photomicrograph.

(Courtesy of Hans E. Grossniklaus, MD.)

Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.