Corneal Dystrophies
Table 10-3 lists the MIM (Mendelian Inheritance in Man) numbers and abbreviations and the IC3D abbreviations.
Table 10-3
Epithelial and Subepithelial Dystrophies
Epithelial basement membrane dystrophy (EBMD)
Alternative names Map-dot-fingerprint dystrophy, Cogan microcystic epithelial dystrophy, anterior basement membrane dystrophy
Inheritance Sporadic (ie, no documented inheritance), thought to be degenerative
Genetics
Category
Unknown
Most cases are sporadic; some are category 1
PATHOLOGY EBMD is an abnormality of epithelial turnover, maturation, and production of basement membrane. Histologic findings include the following:
a thickened basement membrane with extension into the epithelium
abnormal epithelial cells with microcysts (often with absent or abnormal hemidesmosomes) fibrillar material between the basement membrane and Bowman layer
CLINICAL FINDINGS EBMD occurs in 6%–18% of the population, more commonly in women, with increasing frequency over the age of 50 years. Gray patches, microcysts, and/or fine lines in the corneal epithelium are seen on examination. These are usually best seen with sclerotic scatter, retroillumination, or a broad tangential beam. Four kinds of abnormalities are seen in the epithelium and its immediately subjacent basement membrane:
1.fingerprint lines
2.map lines
3.dots or microcysts
4.bleb or cobblestone-like pattern
These abnormalities occur in varying combinations and can change in number and distribution over time. Fingerprint lines are thin, relucent, hairlike lines; several of them can be arranged in a concentric pattern so they resemble fingerprints. Map lines are the same as fingerprint lines except thicker, more irregular, and surrounded by a faint haze; they resemble irregular coastlines or geographic borders on maps (Fig 10-1). Maps and fingerprints consist of thickened or multilaminar strips of epithelial basement membrane. Dots are intraepithelial spaces containing the debris of epithelial cells that have collapsed and degenerated before having reached the epithelial surface (Fig 10-2). The gray-white dots have discrete edges.
Figure 10-1 Epithelial basement membrane dystrophy, showing thick geographic map lines, or “putty marks.”
Figure 10-2 Epithelial basement membrane dystrophy, showing microcysts and geographic map line areas. (Courtesy of Vincent
P. deLuise, MD.)
Symptoms that are related to recurrent epithelial erosions and to transient blurred vision are more common in patients older than 30 years but can be seen at any age. It is estimated that 10% of patients with EBMD will have corneal erosions and that 50% of patients with recurrent epithelial erosions have evidence of this anterior dystrophy. Basement membrane changes in the visual axis can cause irregular astigmatism and blurred vision. Both eyes must be examined because evidence of the dystrophy may be found in the uninvolved eye. Unilateral epithelial basement membrane changes may be related to localized trauma rather than a dystrophy. In some cases, clinical findings may mimic corneal intraepithelial dysplasia, and removed material should be submitted for histology.
MANAGEMENT Asymptomatic patients may not require treatment. For patients with irregular astigmatism, corneal debridement may be necessary. See Chapter 3 for discussion of recurrent erosions.
Mutation in keratin genes: Meesmann epithelial corneal dystrophy (MECD)
Alternative names Juvenile hereditary epithelial dystrophy; variant: Stocker-Holt
Inheritance Autosomal dominant
Genetics Locus 12q13; gene: keratin K3 (KRT3); Stocker-Holt variant: locus 17q12; gene: keratin K12 (KRT12)
Category 1 (including the Stocker-Holt variant)
PATHOLOGY In MECD, epithelial microcysts consisting of degenerated epithelial cell products are present (PAS-positive cellular debris that fluoresces). The epithelial cells contain an electron-dense accumulation of granular and filamentary material (“peculiar substance”). There are frequent mitoses and a thickened basement membrane with projections into the basal epithelium; the basal epithelial cells have increased glycogen. On confocal microscopy, hyporeflective areas are seen in the basal epithelium ranging from 40 to 150 μm in diameter, with potential reflective spots inside.
CLINICAL FINDINGS MECD appears very early in life. Tiny epithelial vesicles are seen—most easily with retroillumination—extending out to the limbus. These appear as tiny, bubble-like blebs and are most numerous in the interpalpebral area (Fig 10-3). The epithelium surrounding the cyst is clear. Whorled and wedge-shaped epithelial patterns may be seen. The cornea may be slightly thinned, and corneal sensation may be reduced. Symptoms are usually limited to mild irritation and a slight decrease in vision. Some patients complain of glare and light sensitivity. Painful recurrent erosions may occur.
Figure 10-3 Meesmann dystrophy, appearing as tiny, bubble-like blebs against the red reflex. (Courtesy of Vincent P. deLuise, MD.)
MANAGEMENT Most patients require no treatment, but soft contact lens wear may be helpful if patients show frequent symptoms.
Tuft S, Bron AJ. Imaging the microstructural abnormalities of Meesmann corneal dystrophy by in vivo confocal microscopy. Cornea. 2006;25(7):868–870.
Lisch epithelial corneal dystrophy (LECD)
Alternative names Band-shaped and whorled microcystic dystrophy of the corneal epithelium
Inheritance
Genetics
Category
X-chromosomal dominant
Locus Xp22.3; gene unknown
2
PATHOLOGY Diffuse cytoplasmic vacuolization of affected cells is seen in light and transmission electron microscopy. On immunohistochemistry, there is scattered staining on Ki67 without evidence of increased mitotic activity. Confocal microscopy shows many solitary dark round and oval lesions (50–100 μm). Some lesions show central reflective points (probably cell nuclei).
CLINICAL FINDINGS On direct slit-lamp examination, discrete sectorial, gray, band-shaped, and feathery lesions appear in whorled patterns. Retroillumination reveals intraepithelial, densely crowded clear microcysts (Fig 10-4). The surrounding epithelium is clear. In Meesmann dystrophy, such band-shaped, feathery lesions do not exist, and the corneal involvement is more diffuse. Also, the intraepithelial cysts of Meesmann are not as densely crowded as in Lisch dystrophy but are isolated, with clear spaces between the cysts.
Figure 10-4 Lisch corneal dystrophy characterized by bands of gray, feathery opacities. Retroillumination shows sectorial, densely crowded clear microcysts in a feathery shape. (Courtesy of Robert W. Weisenthal, MD.)
MANAGEMENT Patients with Lisch dystrophy are pain-free. There may be an associated decrease in vision. Corneal debridement may be attempted but often results in recurrence. Contact lenses may be helpful for more severe cases.
Alvarez-Fischer M, de Toledo JA, Barraquer RI. Lisch corneal dystrophy. Cornea. 2005;24(4):494–495.
Lisch W, Büttner A, Oeffner F, et al. Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to xp22.3. Am J Ophthalmol. 2000;130(4):461–468.
Gelatinous droplike corneal dystrophy (GDLD)
Alternative names Subepithelial amyloidosis, primary familial amyloidosis
Inheritance Autosomal recessive
Genetics
Category
Locus 1p32; gene: tumor-associated calcium signal transducer 2 (TACSTD2)
1
PATHOLOGY Light microscopy shows subepithelial and stromal amyloid deposits. Disruption of epithelial tight junctions leads to abnormally high epithelial permeability. Amyloid deposition is noted in the basal epithelial layer on transmission electron microscopy.
CLINICAL FINDINGS Onset occurs in the first to second decade of life with subepithelial lesions that may appear similar to band keratopathy or with groups of multiple small nodules (mulberry configuration) (Fig 10-5). The lesions are visible on fluorescein staining. There is a significant decrease in vision, with photophobia, irritation, and tearing, and a progression of protruding subepithelial lesions. Superficial vascularization is often seen. Stromal opacification or larger nodular lesions (kumquat-like lesions) may develop (see Fig 10-5C).