Fuchs' dystrophy

Overview
Fuchs' dystrophy, also known as Fuchs' endothelial dystrophy, is a slowly progressing corneal disease that usually affects both eyes and is slightly more common in women than in men. Although doctors can often see early signs of Fuchs' dystrophy in people in their 30s and 40s, the disease rarely affects vision until people reach their 50s and 60s.

The condition was first described by Austrian Ernst Fuchs (1851-1930), for whom it is named.

Etiology
Fuchs’ endothelial dystrophy (FED) is a progressive disorder of the corneal endothelium with accumulation of focal excrescences called guttae and thickening of Descemet’s membrane, leading to corneal edema and loss of vision. The cornea is the outermost portion of the eye that overlies the anterior chamber, iris, and lens apparatus. Clarity of the cornea is necessary for visual function. The normal human cornea contains the following layers: epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. Corneal endothelial cells are the major “pump” cells of the cornea to allow for stromal clarity. In FED, Descemet’s membrane is grossly thickened with accumulation of abnormal wide-spaced collagen and numerous guttae. Corneal endothelial cells in end-stage FED are reduced in number and appear attenuated, causing progressive stromal edema. Progressive endothelial cell loss causes relative influx of aqueous humor into the cornea, leading to swelling (corneal stromal edema), with resultant distorted vision. Eventually, the epithelium also becomes edematous, resulting in more severe visual impairment. Focal areas or blisters of epithelial edema ("bullae") may be particularly painful.

The inheritance of FED is autosomal dominant with genetic and environmental modifiers such as increased prevalence in the elderly and in females. Endothelial cell loss may be aggravated or accelerated by intraocular trauma or surgery. A common scenario involves excessive corneal swelling or edema following cataract surgery or other types of ocular surgery. Hence, patients with a history of Fuchs' dystrophy may be at a greater risk of corneal edema after ocular surgery as they have less functioning endothelial cells.

FED is classified into 4 stages, from early signs of guttae formation to end-stage subepithelial scarring. Diagnosis is made by biomicroscopic examination; other modalities, such as corneal pachymetry, confocal biomicroscopy, and specular microscopy can be used in conjunction. Exact pathogenesis is unknown but factors include endothelial cell apoptosis, sex hormones, inflammation, and aqueous humor flow and composition. Mutations in collagen VIII, a major component of Descemet’s membrane secreted by endothelial cells, have been linked to FED.

Signs and symptoms
At first, a person with Fuchs' dystrophy will awaken with blurred vision that will gradually clear during the day. This occurs because the cornea is normally thicker in the morning; it retains fluids during sleep that evaporate in the tear film while we are awake. As the disease worsens, this swelling will remain constant and reduce vision throughout the day.

Treatment
Medical management includes topical hypertonic saline, the use of a hairdryer to dehydrate the precorneal tear film, and therapeutic soft contact lenses. In using a hairdryer, the patient is instructed to hold a hairdryer at an arm's length or directed across the face, to dry out the epithelial blisters. This can be done two or three times a day. Definitive treatment, however, (especially with increased corneal edema) is surgical in the form of corneal transplantation, or penetrating keratoplasty (PKP). New surgical modalities are gaining popularity in the treatment of FED such as deep lamellar endothelial keratoplasty (DLEK) and Descemet’s stripping with endothelial keratoplasty (DSEK). DLEK and DSEK avoid the surgical complications of PKP such as wound dehiscence and infections and high postoperative astigmatism. Future directions in the treatment of FED include in vitro expansion of human corneal endothelial cells for transplantation and genetic modification.