Fuchs endothelial corneal dystrophy

Synonyms

2

Overview

Fuchs endothelial corneal dystrophy (FECD) is an eye disease. It affects the thin layer of cells that line the back part of the cornea. This layer is called the endothelium. The disease occurs when these cells slowly start to die off. The cells help pump excess fluid out of the cornea. As more and more cells are lost, fluid begins to build up in the cornea, causing swelling and a cloudy cornea. There are several forms of the disease according to the age of onset of the symptoms and the cause.

The early-onset form is very rare and is known as Fuchs endothelial corneal dystrophy 1 (or early-onset Fuchs endothelial corneal dystrophy) and it is caused by a change (mutation) in the COL8A2 gene. Late-onset Fuchs endothelial corneal dystrophies are common and include:

  • Fuchs endothelial corneal dystrophy 2 (caused by a mutation in an unknown gene located in chromosome 13)
  • Fuchs endothelial corneal dystrophy 3 (may be caused by TCF4 gene mutations)
  • Fuchs endothelial corneal dystrophy 4 (caused by a mutation in the SLC4A11 gene)
  • Fuchs endothelial corneal dystrophy 5 (caused by a mutation in an unknown gene located in chromosome 15)
  • Fuchs endothelial corneal dystrophy 6 (caused by a mutation in the ZEB1 gene)
  • Fuchs endothelial corneal dystrophy 7 (caused by a mutation in an unknown gene located in chromosome 9)
  • Fuchs endothelial corneal dystrophy 8 (caused by heterozygous mutation in the AGBL1 gene).

Early in the disease, patients typically do not have symptoms. In the late-onset forms, the symptoms start around 50 or 60 years and include discomfort and painful episodes of recurrent corneal wounds and hazy vision. Over time, discomfort may diminish but severe impairment of visual acuity, and even blindness and cataracts in elderly patients, may be observed. Once the vision has worsened, the recommended treatment is a penetrating graft which has excellent results in most cases.[

Symptoms

The person with this disease is awaken with blurred vision and complaints of glare that gradually improve during the day. This occurs because the cornea is normally thicker in the morning; it retains fluids during sleep due to our eyelids being closed, and that fluid in the cornea evaporates while we are awake. As the disease worsens, this swelling will remain persistent and reduce vision throughout the day. Researchers are finding that Fuchs' is a genetically heterogeneous disease, and many different genes and loci have been associated as contributing to a small percentage of overall Fuchs' cases. Certain genetic lesions have been correlated with more severe disease and earlier onset. Therefore some individuals may experience symptoms of the disease at a much earlier age, while others may not experience symptoms until late in life.

The followings are common symptoms regarding this disease;

  • Corneal dystrophy
  • Impaired vision
  • Corneal clouding
  • Corneal swelling
  • Blurry vision

Causes

The inheritance of Fuchs dystrophy is not straight forward. In some cases, Fuchs dystrophy appears to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When this condition is caused by a mutation in the COL8A2 gene (which is the early-onset form of the disease), it is inherited in an autosomal dominant pattern. In addition, an autosomal dominant inheritance pattern is seen in some situations in which the condition is caused by changes in an unknown gene. However, in many cases, the inheritance pattern is unknown. Some cases result from new mutations in a gene and occur in people with no history of the disorder in their family. Due to the complex nature of the inheritance of this condition, we strongly recommend you discuss your concerns with a genetics professional.

The genetics of Fuchs endothelial dystrophy are unclear. Researchers have identified regions of a few chromosomes and several genes that they think may play a role in the development of Fuchs endothelial dystrophy, but many of these associations need to be further tested.
Fuchs endothelial dystrophy affects a thin layer of cells that line the back of the cornea, called corneal endothelial cells. These cells regulate the amount of fluid inside the cornea. An appropriate fluid balance in the cornea is necessary for clear vision. Fuchs endothelial dystrophy occurs when the endothelial cells die, and the cornea becomes swollen with too much fluid. Corneal endothelial cells continue to die over time, resulting in further vision problems. It is thought that mutations in genes that are active (expressed) primarily in corneal endothelial cells or surrounding tissue may lead to the death of corneal endothelial cells, resulting in Fuchs endothelial dystrophy.

Diagnosis

The diagnosis of Fuchs' endothelial dystrophy is clinical. The diagnosis is relatively easy in early disease as you can see the endothelial changes as will as mild corneal stromal edema. In severe cases where you cannot see the endothelium the diagnosis can be more challenging and the diagnosis may need to be based on the contra lateral eye or history.

The differential diagnosis for Fuchs' endothelial dystrophy includes anything that could induce endothelial deposits and/or corneal swelling. This includes: Pigment dispersion syndrome Keratic precipitates from uveitis Herpetic stromal keratitis Pseudophakic or aphakic bullous keratopathy Iridocorneal endothelial (ICE) dystrophy Congenital hereditary endothelial dystrophy Congenital stromal dystrophy Toxic anterior segment syndrome Posterior Polymorphic Membrane Dystrophy.

Prognosis

The prognosis for both penetrating keratoplasty and DSEK is excellent in the patients with Fuchs' dystrophy. Both procedures will allow for recovery of excellent vision and a normal lifestyle.

Treatment

The treatment of FCED is utilized to treat symptoms of early disease. 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. It has also been reported that botulinum toxin can produce improvement lasting several months. Definitive treatment, however, (especially with increased corneal edema) is surgical in the form of corneal transplantation.

Resources

  • NIH
  • Genetics Home Reference