Figure 6-19 Corneal blood staining. A, Clinical appearance. B, Masson trichrome stain. The red particles represent erythrocytic debris and hemoglobin in the corneal stroma. C, An iron stain demonstrates hemosiderin (arrows), confined to

the stromal keratocytes. (Part A courtesy of Anthony J. Lubniewski, MD; parts B and C courtesy of Hans E. Grossniklaus, MD.)

Dystrophies

Dystrophies of the cornea are primary, generally inherited, bilateral disorders, categorized by the layer of the cornea most involved (ie, epithelial, stromal, endothelial). Keratoconus (previously discussed) may be considered a dystrophy, except that it is often sporadic and likely multifactorial in etiology. Only the most common corneal dystrophies are discussed in the following sections. See also BCSC Section 8, External Disease and Cornea.

Epithelial dystrophy

Also called map-dot-fingerprint dystrophy, Cogan microcystic dystrophy, anterior basement membrane dystrophy (ABMD), and epithelial basement membrane dystrophy (EBMD), epithelial dystrophy may be the most common of the corneal dystrophies seen by the comprehensive ophthalmologist (Fig 6- 20). It is often sporadic but may be inherited in an autosomal dominant fashion. In this condition, the basement membrane is thickened and may extend into the epithelium (forming “map” and “fingerprint” lines). The intraepithelial basement membrane redundancies may encircle foci of epithelial cells, which may then degenerate, resulting in epithelial debris within cystoid spaces (“dots”) (Fig 6-20C). Patients with epithelial dystrophy often present with symptoms of recurrent erosion syndrome.

Figure 6-20 Epithelial basement membrane dystrophy (EBMD, map-dot-fingerprint dystrophy). A, Clinical appearance depicting fine, lacy opacities (arrows). B, Retroillumination demonstrating wavy lines (arrow) and dotlike lesions (arrowhead). C, The changes in primary map-dot-fingerprint dystrophy are essentially identical to those seen in cases of chronic corneal edema secondary to endothelial decompensation. Note the intraepithelial basement membrane (BM) and the degenerating epithelial cells trapped within cystoid spaces (C). D, When surgical treatment is required for EBMD, removal of abnormal epithelium (superficial keratectomy) may be performed, as in this case. PAS stain highlights numerous folds (arrowheads) in

the epithelial basement membrane. (Part A courtesy of Andrew J.W. Huang, MD; part D courtesy of George J. Harocopos, MD.)

Stromal dystrophies

The corneal stromal dystrophies presented in the following subsections (macular, granular, lattice, Avellino) are all inherited disorders and may present with symptoms of decreased vision and recurrent erosion syndrome. All of the stromal dystrophies may recur in corneal grafts.

The genetics of the stromal dystrophies have become elucidated in recent years, enhancing our understanding of these disorders. At the same time, the genetic discoveries raise questions regarding the proper classification of the corneal dystrophies: the same dystrophy may be associated with multiple different mutations, while the same mutation may result in multiple different clinical phenotypes. The International Committee for Classification of Corneal Dystrophies (IC3D) was created for the purpose of devising a current, accurate, and uniform nomenclature. The information

given in the following subsections reflects the current IC3D nomenclature. The IC3D classification is available on the website of The Cornea Society (www.corneasociety.org/publications/ic3d).

Weiss JS, Møller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27(Suppl 2):S1–S80.

Macular dystrophy Macular dystrophy, an autosomal recessive stromal dystrophy, involves the entire cornea (ie, limbus to limbus) and may involve the full thickness of the cornea, including the endothelium. Clinically, it is characterized by poorly defined stromal lesions (focal opacities) with hazy intervening stroma. Mucopolysaccharide material is deposited both intracellularly and extracellularly in the corneal stroma (Fig 6-21). The material stains blue with alcian blue and colloidal iron stains, with the majority of mucopolysaccharide deposits seen in the interlamellar spaces and in keratocytes. Corneal thinning may occur as well. The number of endothelial cells may be decreased, and guttae may be seen in the Descemet membrane. Macular dystrophy is caused by mutations in the carbohydrate sulfotransferase 6 gene (CHST6) on chromosome 16 (16q22), which is responsible for the sulfation of keratan sulfate. Numerous different mutations in this gene have been described in macular dystrophy, with certain mutations having greater prevalence in specific regions of the world.

Figure 6-21 Macular dystrophy. A, Clinical appearance depicting diffusely hazy cornea with focal opacities. B, H&E stain. Note the clear spaces surrounding the keratocytes and in the stroma. C, Colloidal iron stains mucopolysaccharides in the

keratocytes and stroma. (Part A courtesy of Sander Dubovy, MD.)

Granular dystrophy Granular dystrophy (type 1) is an autosomal dominant stromal dystrophy that involves the central cornea and has sharply defined lesions with clear intervening stroma (Fig 6-22).

Histologically, irregularly shaped, well-circumscribed deposits of hyaline material are visible in the stroma. This material stains bright red with the Masson trichrome stain. The mutation causing granular dystrophy occurs in the TGFβI (βig-h3 = BIGH3 = keratoepithelin) gene on chromosome 5 (5q31). Several different mutations in this gene have been described in association with granular dystrophy.

within the corneal stroma (Fig 6-24). This autosomal dominant dystrophy, like granular and lattice dystrophy, has been attributed to mutations in the BIGH3 gene on 5q31. See Table 6-2 for a histologic comparison of macular, granular, lattice, and Avellino dystrophies.

Table 6-2

Figure 6-24 Avellino dystrophy. A, Clinical appearance, showing 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 the Bowman layer and anterior stroma (arrowheads). Other deposits at various levels of the stroma stain a darker blue than the stromal background (triple arrow); these deposits were found on Congo red stain to be amyloid. (Part A modified with permission from Krachmer JH, Palay

DA. Cornea Atlas. 2nd ed. Philadelphia: Mosby-Elsevier; 2006:163. Part B courtesy of George J. Harocopos, MD.)

Endothelial dystrophy

Fuchs dystrophy is inherited in an autosomal dominant fashion or may be sporadic. It is one of the leading causes of bullous keratopathy (discussed earlier). Its defining characteristic is the presence of anvil-shaped excrescences of Descemet membrane, called guttae, which protrude into the anterior chamber or may be buried within a thickened Descemet membrane (Fig 6-25). Guttae may be recognized clinically in young adulthood, long before the cornea decompensates. Over time, progressive endothelial cell loss occurs, ultimately resulting in visually significant corneal edema and bullous keratopathy, typically in middle-aged to older individuals. As in bullous keratopathy from other causes, there are varying degrees of secondary epithelial basement membrane changes and subepithelial fibrosis, similar to changes seen in map-dot-fingerprint dystrophy. In cases of endothelial decompensation without extensive subepithelial fibrosis, endokeratoplasty rather than