Epithelial–Stromal TGFBI Dystrophies
A mutation in the TGFBI gene, located at 5q31, results in the most common corneal dystrophies that involve both epithelium and stroma. TGFBI encodes keratoepithelin, a protein elaborated predominantly by the corneal epithelium. Thus, these dystrophies arise in the epithelium, and the stroma is involved secondarily in their pathogenesis.
Reis-Bücklers corneal dystrophy
Reis-Bücklers corneal dystrophy (RBCD; formerly known as corneal dystrophy of Bowman layer type I, among other names) is an autosomal dominant disorder characterized by confluent irregular, coarse, and angulated geographic-like opacities with varying densities at the level of Bowman layer and the superficial stroma (Fig 6-18A). OCT demonstrates a homogeneous, confluent layer of hyperreflective deposits, often with a serrated anterior border, at the level of Bowman layer and the anterior stroma. Histologically, the Bowman layer is replaced by material comprising a multilayered pannus, which stains intensely red with Masson trichrome stain (Fig 6-18B) and immunoreacts with anti-TGFBI antibodies. The overlying epithelium is irregular in thickness. Ultrastructural studies show crystalloids that stain deeply black with osmium tetroxide, resembling those in granular corneal dystrophy.
Figure 6-17 Epithelial basement membrane dystrophy (EBMD, also called map-dot-fingerprint dystrophy). A, Clinical photograph showing fine, lacy opacities (arrows).B, Retroillumination demonstrating wavy lines (arrow) and dotlike lesions (arrowhead).C, The changes in primary EBMD are essentially identical to those observed in the epithelium in cases of chronic corneal edema secondary to endothelial decompensation. Note the intraepithelial basement membrane (BM) highlighted with PAS stain 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 irregular, wavy thickening (arrowheads) of the epithelial basement membrane.
(Part A courtesy of Andrew J.W. Huang, MD; part D courtesy of George J. Harocopos, MD.)
Thiel-Behnke corneal dystrophy
Thiel-Behnke corneal dystrophy (TBCD; formerly known as corneal dystrophy of Bowman layer type II, among other names) manifests clinically as solitary flecks or irregularly shaped, scattered opacities at the level of Bowman layer that progress to symmetric subepithelial honeycomb opacities. OCT demonstrates prominent hyperreflective material at the level of Bowman layer that extends into the epithelium in a characteristic sawtooth pattern. Histologic evaluation shows diffuse replacement of Bowman layer by fibrous pannus and the sawtooth pattern observed with OCT (Fig 6-19). Ultrastructurally, the abnormal material in TBCD is composed of curly collagen fibers that are approximately 10 nm in diameter and distinctly different from the deposits in RBCD.
Figure 6-18 Reis-Bücklers corneal dystrophy. A, Clinical photograph shows coarse opacities resembling a geographic map in the superficial cornea. Note the circumferential linear scar in the peripheral cornea associated with a lamellar graft, in this case of recurrent corneal dystrophy. B, Masson trichrome stain demonstrates diffuse loss of Bowman layer, superficial stromal fibrosis, and numerous red deposits (arrows).
(Part A courtesy of Brandon Ayres, MD; part B courtesy of Tatyana Milman, MD.)
Figure 6-19 Thiel-Behnke corneal dystrophy. Masson trichrome stain demonstrates diffuse replacement of Bowman layer by a thick fibrous pannus (bracket). The overlying epithelium exhibits a sawtooth configuration. The underlying stroma appears to be uninvolved.
(Courtesy of Tero Kivelä, MD.)
Lattice corneal dystrophy type 1
Classic lattice corneal dystrophy (LCD), or LCD type 1 (LCD1), is an autosomal dominant stromal dystrophy characterized by branching, refractile lines in the central corneal stroma, as well as intervening stromal haze in the later stages of disease (Fig 6-20A). Histologic examination reveals poorly demarcated, fusiform amyloid deposits, most conspicuously in the anterior stroma and Bowman layer (Fig 6-20B). These deposits stain red orange with Congo red on standard light microscopy and exhibit apple-green birefringence (dichroism, ie, 2 different colors depending on lighting conditions) under polarized light (Fig 6-20C, D).
Figure 6-20 Lattice corneal dystrophy type 1. A, Clinical photograph. Note the fine lattice lines (arrows).B, H&E stain shows scattered fusiform, eosinophilic deposits in the anterior and midstroma. C, Congo red stain (red orange) demonstrates that the fusiform deposits are amyloid. D, With Congo red stain, under polarized light, amyloid deposits exhibit apple-green birefringence (dichroism).
(Parts B–D courtesy of Hans E. Grossniklaus, MD.)
Granular corneal dystrophy type 1
Granular corneal dystrophy type 1 (GCD1) is an autosomal dominant disorder characterized by sharply demarcated (granular) central corneal stromal deposits separated by clear intervening stroma (Fig 6-21A). Histologically, irregularly shaped, well-circumscribed, crumblike deposits of hyaline material, which stain bright red with Masson trichrome, are visible in the stroma (Fig 6-21B, C).
Granular corneal dystrophy type 2
Formerly known as Avellino dystrophy, GCD type 2 (GCD2) demonstrates clinical, histologic, and ultrastructural features of both GCD1 and LCD1 (Fig 6-22).
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.