Figure 7-5 A, Clinical photograph of the anterior segment in a patient with Axenfeld-Rieger syndrome. Iris atrophy, polycoria, and iris strands in the periphery are present. Posterior embryotoxon can be seen laterally (arrows). B, Gross photograph shows a prominent Schwalbe line and the anterior insertion of iris strands (Axenfeld anomaly). C, Light micrograph shows
iris strands that insert anteriorly on the Schwalbe line (arrow). (Part A courtesy of Wallace L.M. Alward, MD. Copyright University of Iowa. Part B courtesy of Robert Y. Foos, MD; part C modified with permission from Yanoff M, Fine BS. Ocular Pathology: A Color Atlas. New York: Gower; 1988.)
Degenerations
Iridocorneal Endothelial Syndrome
Iridocorneal endothelial (ICE) syndrome refers to a spectrum of acquired unilateral abnormalities of the corneal endothelium, anterior chamber angle, and iris typically affecting young to middle-aged adults. Three clinical variants are recognized (the first letter of each type, when combined, forms the mnemonic ICE):
iris nevus (Cogan-Reese) syndrome
Chandler syndrome essential iris atrophy
Epithelial-like metaplasia and abnormal proliferation of the corneal endothelium are constant features of all forms of the ICE syndrome. Abnormal endothelial cells migrate over the anterior chamber angle, leading to peripheral anterior synechiae (PAS) formation and subsequent secondary angle-closure glaucoma in approximately half of the patients with this condition (Fig 7-6). See BCSC Section 8, External Disease and Cornea, and Section 10, Glaucoma, for further discussion.
Levy SG, McCartney AC, Baghai MH, Barrett MC, Moss J. Pathology of the iridocorneal-endothelial syndrome. The ICE-cell.
Invest Ophthalmol Vis Sci. 1995;36(13):2592–2601.
Figure 7-6 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, nevuslike appearance (arrowheads). B, Essential iris atrophy. Atrophic holes in the iris and a narrow anterior chamber, consistent with PAS formation. C, A membrane composed of spindle cells lines the posterior surface of the cornea and the anterior surface of the atrophic iris (arrows). These metaplastic endothelial cells deposit on the iris surface a thin basement membrane that has a positive periodic acid–Schiff reaction and is analogous to the 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.)
Secondary Glaucoma With Material in the Trabecular Meshwork
Exfoliation syndrome
Also known as pseudoexfoliation, exfoliation syndrome is a systemic condition that is usually identified in individuals older than 50 years and is 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 (Fig 7-7). These deposits distinguish exfoliation syndrome from true exfoliation, which is the splitting of the lens capsule induced by infrared radiation.
Recent data support the pathogenic concept of exfoliation syndrome as a type of stress-induced elastosis associated with the excessive production and abnormal aggregation of elastic fiber components. Mutations in the lysyl oxidase–like 1 gene, LOXL1, on chromosome 15 (15q24) were found to be a major genetic risk factor for exfoliation syndrome. Lysyl oxidase is a pivotal enzyme in extracellular matrix formation, catalyzing covalent crosslinking of collagen and elastin.
Exfoliative material is most apparent on the surface of the anterior segment structures, where it exhibits a positive periodic acid–Schiff reaction and presents as delicate, feathery or brushlike fibrils arranged perpendicular to the surfaces of the intraocular structures (Fig 7-8A, B). Exfoliative material also accumulates in the trabecular meshwork and the wall of the Schlemm canal. Associated degenerative changes in the iris pigment epithelium are manifested histologically by a “saw-toothed” configuration (Fig 7-8C). See also BCSC Section 10, Glaucoma, and Section 11, Lens and Cataract.
Schlötzer-Schrehardt U. Molecular pathology of pseudoexfoliation syndrome/glaucoma—new insights from LOXL1 gene associations. Exp Eye Res. 2009;88(4):776–785.
Phacolytic glaucoma
The condition known as phacolytic glaucoma occurs when denatured lens protein leaks from a hypermature cataract through an intact but permeable lens capsule. The trabecular meshwork becomes occluded by both the lens protein and the macrophages engorged with phagocytosed proteinaceous, eosinophilic lens material (Fig 7-9).
Figure 7-7 Gross photograph shows fibrillar deposits on the lens zonular fibers (arrows) in exfoliation syndrome (pseudoexfoliation).
Figure 7-8 Exfoliation syndrome (pseudoexfoliation). A, Abnormal material appears on the anterior lens capsule like iron filings on the edge of a magnet (arrows). B, Note the pigmentation and small clumps of eosinophilic pseudoexfoliative material (arrow) in the anterior chamber angle. C, The iris pigment epithelium demonstrates a “saw-toothed” configuration,
consistent with pseudoexfoliation. (Part C courtesy of Tatyana Milman, MD.)
Trauma
Following an intraocular hemorrhage, blood breakdown products may accumulate in the trabecular meshwork. The spherical shape and rigidity of hemolyzed erythrocytes make it difficult for them to escape through the trabecular meshwork, leading to ghost cell glaucoma (Fig 7-10).
Figure 7-9 Phacolytic glaucoma. A, Low magnification of macrophages filled with degenerated lens cortical material in the angle. B, Higher magnification.
Figure 7-10 Aqueous aspirate demonstrating numerous ghost red blood cells. The degenerating hemoglobin is present as small globules known as Heinz bodies (arrows). (Courtesy of Nasreen A. Syed, MD.)
In hemolytic glaucoma, macrophages in the anterior chamber have been noted to phagocytose erythrocytes and their breakdown products. These hemoglobin-laden and hemosiderin-laden macrophages block the trabecular outflow channels (Fig 7-11). It is possible that macrophages are 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 examination has revealed hemosiderin within the trabecular endothelium and within many ocular epithelial structures (see Fig 7-11). The presence of hemosiderin may be a sign of damage that occurred during oxidation of hemoglobin. The iron stored in the cells may be an enzyme toxin that damages trabecular function in hemosiderosis oculi. Iron deposition in hemosiderosis oculi can be demonstrated by means of the Prussian blue reaction.
Figure 7-11 Hemolytic glaucoma. The anterior chamber angle is filled with degenerated red blood cells and macrophages containing rust-colored intracytoplasmic material, hemosiderin (arrows). Hemosiderin is also observed within the trabecular
meshwork endothelium (arrowheads). (Courtesy of Tatyana Milman, MD.)
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 pathogenesis of glaucoma after injury. See the section Histologic Sequelae of Ocular Trauma in Chapter 2.
Pigment dispersion associations
Pigment dispersion may be associated with a variety of other conditions in which pigment epithelium or uveal melanocytes are injured, such as uveitis or uveal melanoma. These conditions are characterized by pigment within the trabecular meshwork and in macrophages littering the angle (Fig 7-12).
Secondary open-angle glaucoma can occur as a result of the pigment dispersion syndrome (Fig 7- 13). This type of glaucoma is characterized by radially oriented defects in the midperipheral iris and pigment in the trabecular meshwork, the corneal endothelium (Krukenberg spindle; see Chapter 6, Fig 6-18), and other anterior segment structures, such as the lens capsule. The dispersed pigment is presumed to be from iris pigment epithelium mechanically rubbed off by contact with lens zonular fibers. See also BCSC Section 10, Glaucoma.
Neoplasia
Melanocytic nevi and melanomas that arise in the iris or extend to the iris from the ciliary body may obstruct the trabecular meshwork (Fig 7-14). See also Chapter 17. In addition, pigment elaborated from melanomas and melanocytomas may be shed into the trabecular meshwork and produce secondary glaucoma (melanomalytic glaucoma) (see Fig 7-12). Occasionally, epibulbar tumors such as conjunctival carcinoma can invade the eye through the limbus, leading to trabecular outflow obstruction and glaucoma. See the section Neoplasia in Chapter 5.
Figure 7-12 Secondary open-angle glaucoma. The trabecular meshwork is obstructed by macrophages that have ingested pigment from a necrotic intraocular melanoma (melanomalytic glaucoma).
Figure 7-13 Pigment dispersion syndrome. A, Gross photograph demonstrating radially oriented transillumination defects in the iris. B, Scheie stripe. Melanin is present on the anterior surface of the lens. C, Note the focal loss of iris pigment epithelium (arrow). Chafing of the zonules against the epithelium may release the pigment that is dispersed in this condition. D, Note the accumulation of pigment in the trabecular meshwork.
Figure 7-14 Photomicrograph shows melanoma cells filling the anterior chamber angle and obstructing the trabecular meshwork. Note the iris pigment epithelium in the lower right corner of the photomicrograph.
MD.)