Descemet Membrane and Endothelial Dystrophies
Fuchs endothelial corneal dystrophy
Although Fuchs endothelial corneal dystrophy (FECD) can be inherited in an autosomal dominant fashion, the mode of inheritance is unknown in most cases. FECD is one of the leading causes of bullous keratopathy (discussed earlier), characterized in its early stage by the presence of guttae along Descemet membrane, which when confluent have a “beaten metal” appearance (Fig 6-24A). In some cases, progressive endothelial cell loss occurs over time, ultimately resulting in visually significant corneal edema and bullous keratopathy, typically in middle-aged and older individuals. Endothelial cell loss and irregular thickening of Descemet membrane are the major histologic features of FECD. Histologically, the irregularly thickened Descemet membrane is studded with anvil-shaped or droplike guttae, which may protrude into the anterior chamber or may be buried within a new layer of basement membrane (Fig 6-24B, C). The epithelium demonstrates changes identical to those of bullous keratopathy from degenerative causes. Ultrastructural studies demonstrate the presence of new wide-spaced collagen, made of collagen type VIII, in the posterior banded layer of Descemet membrane and in the guttae. Treatment is surgical, with either PK or, more commonly, EK.
Congenital hereditary endothelial dystrophy
Congenital hereditary endothelial dystrophy (CHED) was traditionally classified as either an autosomal dominant (CHED1) or an autosomal recessive (CHED2) variant. This classification was recently revisited and modified, and the updated IC3D classification eliminates CHED1 as new evidence suggests that this entity be classified as part of the posterior polymorphous corneal dystrophy spectrum (see the following section). CHED2 is now known simply as CHED. A mutation in the SLC4A11 gene, located at 20p13, has been implicated in this dystrophy.
Table 6-1 Histologic Differentiation of Common Anterior Corneal Dystrophies
CHED presents early in life with diffuse or ground-glass, milky, and frequently asymmetric corneal clouding associated with marked corneal thickening (Fig 6-25A). The primary abnormality in CHED is thought to be a degeneration of endothelial cells during or after the fifth month of gestation. Histologically, the Descemet membrane is diffusely thickened and occasionally multilaminated. There is marked loss of endothelial cells (Fig 6-25B).
Posterior polymorphous corneal dystrophy
Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant dystrophy that typically manifests early in life, frequently with asymmetric opacities of various shapes at the level of Descemet membrane, including nummular, vesicular (blisterlike), and “railroad track”–like lesions (Fig 6-26A). The condition can be progressive and can be associated with corneal edema, peripheral iridocorneal adhesions, and IOP elevation. Histologically, Descemet membrane is thickened and multilaminated with focal nodular and fusiform excrescences. Although the corneal endothelium is generally atrophic, overlapping or multilayered aggregates of endothelial cells with spindle morphology may be present focally (Fig 6-26B). These transformed endothelial cells demonstrate the immunophenotypic and ultrastructural features of epithelial cells (ie, epithelialization of the endothelium) with aberrant expression of cytokeratins (CKs) such as CK19, CK5/6, and CK903.
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Aldave AJ, Han J, Frausto RF. Genetics of the corneal endothelial dystrophies: an evidence-based review. Clin Genet. 2013;84(2):109–119.
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Schmedt T, Silva MM, Ziael A, Jurkanas U. Molecular bases of corneal endothelial dystrophies. Exp Eye Res. 2012;95(1):24–34.
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.