The IC3D classification of the corneal dystrophies

Abstract

Background: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis.

Purpose: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis.

Methods: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature.

Results: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available.

Conclusions: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.

FIGURE 1

Epithelial basement membrane dystrophy. A, Map-like changes. B, Intraepithelial dot opacities underlying map-like figures. C, Fingerprint lines viewed in retroillumination.

FIGURE 2

Epithelial recurrent erosion corneal dystrophy (Smolandiensis variant). The right eye of a 41 -year -old female with a central keloid-like opacification found in half of the affected family members.

FIGURE 3

Subepithelial mucinous corneal dystrophy. Subepithelial opacities and haze involving the entire cornea; these are most dense toward the center (broad oblique and slit views).

FIGURE 4

Meesmann corneal dystrophy. A, Multiple solitary microcysts that are most prominent in the interpalpebral region are seen in retroillumination. B, Diffuse gray opacity with broad oblique illumination, and multiple solitary microcysts in retroillumination.

FIGURE 5

Lisch epithelial corneal dystrophy. A, Localized, whorl-like gray opacity on direct illumination. B, Sclerotic scatter demonstrating localized whorl-like gray opacity. C, Retroillumination demonstrating crowded microcysts.

FIGURE 6

Gelatinous drop-like corneal dystrophy. A, Mulberry type. B, Band keratopathy type. C, Kumquat-like type.

FIGURE 7

Reis–Bücklers corneal dystrophy. A, Coarse geographic opacity of the superficial cornea. B, Broad oblique illumination demonstrating dense, reticular, superficial opacity. C, Slit lamp view demonstrating irregularities in Bowman layer.

FIGURE 8

Thiel–Behnke corneal dystrophy. A, Reticular honeycomb pattern of Thiel–Behnke with genetic confirmation of Arg555Gin in TGFBI. B, Superficial opacification in advanced disease.

FIGURE 9

Grayson–Wilbrandt corneal dystrophy. A, Irregularly shaped opacities scattered throughout the entire corneal surface best seen in diffuse illumination. B, Irregular opacities from Bowman layer extending into and involving the epithelium with prominent corneal nerves (images reprinted with permission from the American Journal of Ophthalmology 1966;61:345–349).

FIGURE 10

Lattice corneal dystrophy, TGFBI type (classic lattice). A, Early lattice corneal dystrophy (LCD1) with dots and lattice lines in retroillumination with genetic confirmation of Arg124Cys in TGFBI. B, Magnified view of lattice lines and dots in LCD1. C, Central opacification in advanced LCD1.

FIGURE 11

Lattice corneal dystrophy, gelsolin type (Meretoja). A, Diffuse lattice lines of the stroma. B, Typical facies of the Meretoja syndrome.

FIGURE 12

Granular corneal dystrophy, type 1. A, Discrete and confluent, axially distributed anterior stromal deposits. B, Diffuse granular opacities in an adult. C, Early subepithelial verticillate opacity in a 6-year old.

FIGURE 13

Granular corneal dystrophy, type 2 (granular–lattice). A, Icicle and star-shaped stromal opacities among disk-shaped opacities in a heterozygote with histopathologic confirmation of granular corneal dystrophy, type 2 (GCD2), and genetic confirmation of R124H mutation. B, Finger-like stars and disks in diffuse and retroillumination. C, Seventeen-year old with few white dots and a family history of GCD2. D, Homozygote with denser and confluent opacities.

FIGURE 14

Macular corneal dystrophy. A, Early macular corneal dystrophy with few central opacities. B, Slit-lamp photograph of advanced macular dystrophy with stromal opacities at multiple levels and diffuse stromal haze. C, More advanced macular dystrophy at higher magnification revealing more numerous and diffuse corneal opacities and stromal haze.

FIGURE 15

Schnyder corneal dystrophy (SCD). A, Central stromal opacity in early SCD without crystals. B, Central subepithelial crystals in early SCD with crystals. C, Central ring-like opacity, prominent peripheral arcus lipoides, and moderate mid-peripheral haze in a middle-aged individual with non crystalline Schnyder. D, Central dense opacity, peripheral arcus lipoides, and prominent mid-peripheral haze. E, Advanced SCD with dense corneal opacification, subepithelial crystals, and peripheral arcus lipoides.

FIGURE 16

Congenital stromal corneal dystrophy: diffuse bilateral clouding with flake-like opacities throughout the stroma.

FIGURE 17

Fleck corneal dystrophy: Dandruff-like opacities seen in 2 different patients throughout the stroma using (A) broad oblique illumination and indirect illumination, and (B) at varying depths in the slit-lamp photograph.

FIGURE 18

Posterior amorphous corneal dystrophy: central deep stromal/pre-Descemet opacity with some degree of peripheral extension interrupted by a clear ring in the mid-peripheral cornea.

FIGURE 19

Central cloudy dystrophy of Francois. A, Axially distributed, polygonal gray-white stromal opacities separated by linear areas of clear cornea. B, Broad beam slit lamp photograph demonstrating central stromal opacities with linear clear areas and “cracked ice” appearance.

FIGURE 20

Pre-Descemet corneal dystrophy: punctate opacities anterior to Descemet membrane demonstrated with indirect illumination and slit lamp beam.

FIGURE 21

Fuchs endothelial corneal dystrophy. A, Central guttae viewed in retroillumination and in the slit beam. B, Cornea guttae as seen in specular reflection. C, Advanced stromal edema. D, Advanced endothelial decompensation with epithelial microcystic and bullous edema.

FIGURE 22

Posterior polymorphous corneal dystrophy. A, Endothelial plaque-like lesions. B, Irregular crater-like figures on Descemet membrane viewed with specular reflection. C, Railroad track opacities as seen in broad oblique illumination and retroillumination.

FIGURE 23

Congenital hereditary endothelial dystrophy. A, CHED1—Milky appearance of cornea with diffuse illumination. B, CHED2—Slit beam photograph demonstrating diffuse stromal thickening in a homozygote individual with SLC4A11 mutations.

FIGURE 24

X-linked endothelial corneal dystrophy. Seven-year-old boy with milk glass appearance of the cornea.