Signs and Symptoms
Late hereditary (Fuchs’) endothelial dystrophy is usually seen in the fifth or sixth decade of life. It is more common in women than men, bilateral, and usually of dominant inheritance. The dystrophy itself stems from the primary malfunction of the corneal endothelium. This ultimately causes the disruption of the corneal dehydration system and consequently a physiologically and optically compromised tissue. Presenting symptoms include decreased vision, foreign body sensation and pain upon waking. Biomicroscopic findings include focal thickenings of the Descemet’s membrane known as corneal guttata, corneal stromal edema, folds in Descemet’s membrane secondary to corneal edema, fine pigment dusting on the corneal endothelium, and in advanced stages, corneal pannus, and bullous keratopathy. In general, corneal dystrophies exhibit familial patterns and have no association with systemic or environmental factors. It is associated with a slightly increased prevalence of open angle glaucoma.

Pathophysiology
The cornea consists of five discrete layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium. When healthy, the endothelial cell layer is a single stratum of hexagonal cells that borders Descemet’s membrane. It shows great metabolic activity and is actively involved in the maintenance of corneal dehydration. Following trauma or injury, the surrounding endothelial cells slide over to the injured area. There is no mitotic activity in the adult endothelium. This focal enlargement and/or change in shape of the endothelial layers can be seen using special biomicroscopic techniques and is called polymegathism and pleomorphism, respectively.

The clinical and histopathological progression of Fuchs’ is complex, but can best be divided into three stages, which usually span 10 to 20 years. In the first stage the patient is initially asymptomatic, but manifests central irregularly distributed guttata warts and geographically arranged pigment dusting. Occasionally, a diffuse brown pigmentation of the central posterior surface is also seen. Histologically, the endothelial cells show degeneration and deposition of abnormal Descemet’s membrane material.

In the second stage the patient develops stromal and epithelial edema, with symptoms of glare and hazy vision. Visual acuity is usually 20/30 or better. As edema increases, the stroma thickens centrally, the opacity spreads peripherally and the epithelium develops bullae, which correspond to intraepithelial lakes of fluid. As stromal edema increases, Descemet’s membrane develops folds and vision falls. Eventually, the benefit of better vision late in the day is lost, the epithelium becomes more bullous, and pain and photophobia develops.

In the third phase, subepithelial connective tissues appears centrally. This is an avascular tissue that does not migrate in from the periphery like pannus, but arises in the central cornea. Clinically, it appears as an irregular, dense, gray, swirling sheet of scar tissue. Histologically, it consists of active fibroblasts and of large and small collagen fibrils between Bowman’s layer and the epithelium. In advanced cases, the stromal edema and epithelial bullae disappear as the stroma scars, and the patient becomes more comfortable even though the visual acuity is severely reduced.

Management
The treatment for Fuchs’ endothelial dystrophy varies, depending upon the severity of the disease, and may range from hypertonic drops to surgical intervention. Patients with early stromal and/or epithelial edema may be treated conservatively at first with 5% sodium chloride drops q.i.d. and 5% sodium chloride ointment at bedtime. (Use of a hair dryer held at arms length from the surface of the cornea, in combination with the hyperosmotic agents, may dry out the corneal surfaces and decrease the time the blur persists.)

A therapeutic soft lens (bandage lens) is beneficial in alleviating patient discomfort. A loosely fitting, flat, high-water content soft contact lens will decrease the irregular astigmatism and the pain from ruptured epithelial bullae. This mode of treatment has made life more pleasant for patients who could not afford corneal transplants or who are awaiting a triple procedure with advancing cataract. Take note that any elevation of IOP forces more fluid into the stroma across the compromised endothelium. Appropriate pressure reduction with topical and or oral ocular antihypertensive medications may decrease the progression and symptoms secondary to corneal edema. Corneal grafts for Fuchs’ dystrophy account for approximately 10 percent of all corneal grafts performed. Generally, if the graft is performed before there is involvement of the peripheral cornea, there is an 80 percent likelihood that the graft will remain clear for two years. Keratoplasty in eyes with narrow angles should include lens removal to avoid angle closure with formation of peripheral anterior synechiae. Patients with both Fuchs’ endothelial dystrophy and cataracts will do well with a combined penetrating keratoplasty and cataract extraction.

Clinical Pearls

• Corneal guttata seen in young, asymptomatic patients are known as Hassall-Henle bodies and are of no clinical significance.

• Excessive central guttata in the absence of corneal edema is termed endothelial cell dystrophy. Endothelial cell dystrophy may remain stable or progress to Fuchs’ dystrophy.

• Differential diagnosis should include posterior polymorphous dystrophy, which is a posterior corneal dystrophy with gray, hazy, scalloped bands, variable corneal edema and iris involvement. Also consider aphakic and pseudophakic bullous keratopathy.

Other reports in this section

• Keratitis Sicca/Dry Eye Syndrome
• Bacterial Keratitis
• Herpes Simplex Keratitis
• Sterile Corneal Infiltrates
• Phlyctenulosis
• Corneal Abrasion & Recurrent Corneal Erosion
• Corneal Foreign Body
• Chemical Burs
• Epithelial Basement Membrane Dystrophy (EBMD)
• Thygeson's Superficial Punctate Keratopathy
• Corneal Laceration
• Salzmann’s Nodular Degeneration
• Fuchs’ Endothelial Dystrophy