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.

Figure 6-22 Granular corneal dystrophy type 2 (formerly known as Avellino dystrophy). A, Clinical photograph shows both lattice lines (1) and granular deposits (2). B, Trichrome stain of deep anterior lamellar keratoplasty (DALK) button highlights hyaline deposits at the level of Bowman layer and the anterior stroma (arrowheads). Other deposits at various levels of the stroma stain a darker blue than the stromal background (triple arrow); Congo red stain (not shown) confirmed that these deposits were amyloid. The large empty spaces in the posterior stroma were caused by pneumatic dissection.

(Part A modified with permission from Krachmer JH, Palay DA. Cornea Atlas. 2nd ed. Mosby-Elsevier; 2006:163. Part B courtesy of George J. Harocopos, MD.)

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.

Figure 6-23 Macular corneal dystrophy. A, Clinical photograph showing a diffusely hazy cornea with focal opacities. B, H&E stain. Note the pale pink, fluffy material within the keratocytes and extracellularly in the stroma. C, Colloidal iron stain showing mucopolysaccharides (nonsulfated glycosaminoglycans) in the keratocytes and stroma. D, Colloidal iron stain highlighting mucopolysaccharides in the corneal endothelium (arrowheads). Note the Descemet membrane excrescences, or guttae (arrow).

(Part A courtesy of Sander Dubovy, MD; part D courtesy of Tatyana Milman, MD.)

Table 6-1 Histologic Differentiation of Common Anterior Corneal Dystrophies

Figure 6-24 Fuchs endothelial corneal dystrophy. A, Slit-lamp illumination of the cornea shows the “beaten metal” appearance of Descemet membrane (arrow).B, Corneal button from PK shows endothelial cell loss, with only a few surviving endothelial cells (E). Numerous guttae are seen in Descemet membrane (arrows). The result of endothelial decompensation is bullous keratopathy. Note the diffuse stromal edema (loss of interlamellar clefts) and epithelial bulla (asterisk).C, Specimen from EK shows scant endothelial cells (E) and numerous guttae (arrows).

(Part A reproduced from External Disease and Cornea: A Multimedia Collection. San Francisco: American Academy of Ophthalmology; 2000. Parts B and C courtesy of George J. Harocopos, MD.)

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.

Figure 6-25 Congenital hereditary endothelial dystrophy. A, Clinical photograph showing bilateral diffuse, severe corneal clouding. B, PAS stain showing diffuse stromal edema with bullous keratopathy (arrow). The Descemet membrane is diffusely thickened, without guttae, and endothelial cells are absent.

(Courtesy of Hans E. Grossniklaus, MD.)

Figure 6-26 Posterior polymorphous corneal dystrophy. A, Clinical photograph showing nummular opacities (arrows) and linear opacities on the endothelial surface. B, Histology showing overlapping and multilayered aggregates of endothelial cells (arrow).

(Part A courtesy of Andrew J.W. Huang, MD; part B courtesy of George J. Harocopos, MD.)

• Aldave AJ, Han J, Frausto RF. Genetics of the corneal endothelial dystrophies: an evidence-based review. Clin Genet. 2013;84(2):109–119.

• 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.