guttae

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.