autosomal dominant

This type of anterior corneal dystrophy is genetically heterogeneous (caused by mutations in more than one locus). Recurrent corneal erosions are the main clinical feature and can begin in the first and second decades.  The epithelium is irregularly thickened while the Bowman layer and basal lamina of the basement membrane have degenerative changes which lead to the clinically evident honeycomb pattern of opacities.  Advanced changes in these tissues eventually leads to some vision loss.

The honeycomb pattern of degenerative changes in the corneal epithelium and Bowman membrane helps to distinguish this disorder from other anterior corneal dystrophies.  These are more prominent centrally with relative sparing of the juxtalimbal areas.  The epithelial basement membrane may be missing in some areas.  Histology is required for a definitive diagnosis with electron microscopy revealing characteristic 'curly' collagen fibrils in the subepithelial and anterior stromal tissues.  These degenerative changes tend to recur even after ablative procedures.

There is a great deal of clinical heterogeneity and the diagnosis is often unclear especially in younger individuals.  No doubt much of this is due to the fact that mutations in the major gene (TGFBI) responsible are also responsible for at least 5 other heritable corneal dystrophies and the argument can be made that all are variants of the same condition (vida infra).

Meesmann corneal dystrophy is a disorder of the epithelium and its basement membrane.  Onset is early, even in the first year of life and begins with irritation and often photophobia.  However, some patients remain asymptomatic for many years.  Vision is usually impacted only to a mild degree as a result of surface irregularities and epithelial cysts, which are concentrated most commonly in the interpalpebral regions.  They may only be visible with slit lamp examination. The cysts are usually in the basal cells and are filled with PAS positive material. They may coalesce to form refractile lines and later in life become more opaque. The basement membrane appears coarse and is often abnormally thick.  Bowman layer and the stroma are unaffected.  Corneal sensitivity is reduced.

Stocker-Holt dystrophy (122100) is often lumped with Meesmann dystrophy and, while it is a clinically similar disease, it is usually caused by a different mutation.  The 20 patients reported by Stocker and Holt in 1954 were descendents from Moravia who settled in North Carolina (Meesmann and Wilke's report in 1939 was based on patients in Holstein, Germany).

Peters anomaly occurs as an isolated malformation but also as a feature of other syndromes.  It is often unilateral.  A wide variety of other ocular findings may occur with Peters anomaly as well. Here we limit our description to 'simple' Peters anomaly in which the findings are limited to the eye having the classic findings of adhesions of the iris to the posterior cornea and a central or paracentral corneal leukoma.  The lens may also be adherent to the cornea and is often opacified to some degree.  Descemet's membrane and portions of the posterior stroma are usually missing as well.  Glaucoma is frequently present.  Importantly, there is a wide range in the presentation of clinical features.

North Carolina macular dystrophy is characterized by central macular defects that are present at birth but rarely progress. The fundus findings are highly variable and are usually more dramatic than expected from the visual acuity, which ranges from 20/40 to 20/200, with an average around 20/50. The clinical findings have been classified into different grades: In Grade I, fine drusen-like lesions at the level of the retinal pigmented epithelium are found in the central macular area. Grade II exhibits central confluent drusen with or without pigmentary changes, retinal pigment epithelium atrophy, disciform scar formation or neovascularization. Grade III is characterized by a well-delineated chorioretinal degeneration with hyperpigmentation at the border of the lesion. A central crater-like lesion that affects all retinal layers, as well as the deep choroidal tissue, is a typical finding. It is surrounded by an elevated ridge, which is 3-4 disc diameters size.  Color vision and electrophysiological testing are usually normal.

Some patients have choroidal neovascularization that may be responsive to anti-vascular endothelial growth factor treatment. 

Although first described in a 4 generation North Carolina family, it has since been found in a variety of ethnic groups and geographic locations.

There are a number of endothelial corneal dystrophies to which Fuchs name has been attached, including two that are early in onset, or even congenital (CHED1; 121700), (CHED2; 217700) and at least three that have an adult onset, one (Fuchs endothelial dystrophy, early onset; 136800) which has a relatively early onset and two considered to have a late onset: the one described here and another known as Fuchs Endothelial Dystropy, Late Onset 2 (613267).  Evidence for multiple distinct types comes from genotyping which reveals considerable genetic heterogeneity in spite of similar phenotypes (see Genetics).  All are progressive and degenerative with various degrees of visual disability.  Most have histologic changes in both the endothelial cells and Descemet membrane.

The entity described here likely is the classical disease described in the older literature.  It is certainly the most common, occurring in 4% of the population over the age of 40 years and for unknown reasons is more often found in females.  Guttae are formed as excrescences of Descemet's membrane and develop initially in the central cornea, beginning about the 5^th decade, gradually increasing in number and size toward the periphery. They tend to be relatively large, sharply peaked and often positioned at the cell-cell junctions of endothelial cells.  These are often best visualized by corneal transillumination.  Histologically, the posterior portion of Descemet membrane contains bundles and sheets of abnormal collagen.  Progressive corneal edema follows as endothelial cells are lost and the remaining ones are unable to maintain normal stromal hydration.  Fingerprint lines may be present.  The corneal edema may involve both stroma and epithelium and in advanced stages may lead to painful epithelial erosions.  The disease is relentless and early blurring of vision progresses to significant visual handicaps often requiring corneal transplantation in the 7^th and 8^th decades.

Corneal guttae are common in older individuals but usually are located more peripherally.  The diagnosis of Fuchs can best be made where the guttae are concentrated centrally and associated with stromal and epithelial edema.

This is one of several adult onset corneal endothelial dystrophy (see Fuchs endothelial corneal dystrophy, late onset, (610158) for more forms of adult Fuchs endothelial dystrophy).  The onset of this type is considerably earlier than in the more common adult onset type (610158) .  Endothelial disease has been noted as early as three years of age but onset is likely later than in the congenital forms (CHED1; 121700), (CHED2; 217700).  In early onset Fuchs dystrophy, most individuals have evident disease by the third and fourth decades and many have advanced disease by the fourth and fifth decades.  The sex ratio among affected individuals is closer to 1:1 in this disorder compared with the more common adult onset type in which the disease is more common in females.

In this early onset disorder the guttae are small and more rounded than those in the later onset endothelial dystrophies, and are closer to the center of the endothelial cells.  The progression of corneal decompensation is temporally similar to that of the late onset dystrophies, resulting in clinically advanced disease within 3 to 4 decades.  The progression of disease has been documented through quantifying the number of guttae over time.   Among 26 patients, the number increased as much as 29.1% over a 30 month period, and an exponential increase was noted after age 50 years.  The inferotemporal quadrant of the cornea had the greatest proportion of guttae.  As in other forms of endothelial corneal dystrophy, Descement's  membrane is thickened and exhibits nodularity with secondary apoptosis of endothelial cells.