Corneal dystrophy is a condition that causes a layer of the cornea to cloud over and impair visual clarity. It is usually a bilateral problem, which means it occurs in both eyes equally. There are more than 20 different forms of inherited corneal dystrophies. A corneal dystrophy can occur in otherwise healthy individuals. Depending on the type of condition and the age of the individual, a corneal dystrophy may either cause no problems, moderate vision impairment, or severe difficulties that require surgery.
Description
The cornea is the outside layer of the eye, and comprises five layers itself, including the outer epithelium, the Bowman's layer, the stroma, or middle, layer that takes up about 90% of the entire cornea, the Descemet's membrane, and the endothelium. In most cases, the central (stromal) layer of the cornea is involved.
Some corneal dystrophies are named after the individual who discovered them, while others are descriptive of the pattern seen with the dystrophy or the location of the disease. The key forms of corneal dystrophy are congenital hereditary endothelial dystrophy (CHED), epithelial basement membrane dystrophy, Fuchs' endothelial dystrophy, granular dystrophy, lattice dystrophy, macular corneal dystrophy, Meesmann's corneal dystrophy, posterior polymorphous dystrophy (PPD), and Reis-Bucklers' dystrophy.
Genetic profile
Genetic alterations (mutations) causing corneal dystrophies have been mapped to 10 different chromosomes. Some dystrophies have not yet been mapped, including Fuchs' dystrophy.
Some corneal dystrophies have the same genetic address. Mutations on the BIGH3 gene of chromosome 5q31 cause granular corneal dystrophy and Reis-Bucklers' dystrophy. Macular corneal dystrophy has been mapped to an altered gene on chromosome 16. The mutation causing congenital hereditary endothelial dystrophy has been mapped to 20p11-20q11. Lattice type I is linked to the 5q31 locus (location), while lattice type II dystrophy is linked to the 9q34 locus. Posterior polymorphous corneal dystrophy has been linked to the 20q11 locus.
Most corneal dystrophies, with the exception of congenital endothelial corneal dystrophy and macular dystrophy, are autosomal dominant. In dominant disorders, a single copy of the mutated gene (received from either parent) dominates the normal gene and results in the appearance of the disease. The risk of transmitting the disorder from parent to offspring is 50% for each pregnancy.
Both congenital endothelial corneal dystrophy and macular dystrophy are autosomal recessive. This means the affected person inherits the same abnormal gene for the same trait from both parents; each parent is a carrier for the disease, but they usually will have no symptoms of the disease. The risk of transmitting the disease to each pregnancy is 25%.
Demographics
The diversity of corneal dystrophies diseases makes it difficult to provide specific demographic data. Some dystrophies appear in early childhood or even infancy, such as Reis-Bucklers' dystrophy. Others may not appear until middle age or beyond, as with Fuchs' dystrophy. Women are at greater risk for Fuchs' dystrophy, especially those over age 40. However, most corneal dystrophies present before age 20.
Signs and symptoms
The symptoms vary with the type of corneal dystrophy and the location of the site. Most experts categorize these diseases based on whether they are located on the anterior (outer) layer, stromal (middle) layer, or endothelial (inner) layer.
Anterior corneal dystrophies
The epithelium, or the "basement membrane," and the Bowman's layer together comprise the anterior, or outer part, of the cornea. Epithelial basement membrane dystrophy, also known as Cogan's map-dot-fingerprint dystrophy, is a disorder that causes errors in refractions of the eye and may also present with microscopic cysts. This disease results from excessive fluid (edema) and swelling of the basement membrane into the epithelium. Symptoms of this disease are map-like dots, opaque circles, or thin lines that are formed in a swirled pattern like fingerprints. Individuals with this disorder feel like they have something irritating in the eye and experience pain and light sensitivity (photophobia).
The tiny opaque collagen fibers that cause Reis-Bucklers' dystrophy create a linear or ring-like pattern. People with this disease have recurrent painful erosions of the cornea and may also suffer from severe visual impairment. Reis-Bucklers' is usually noticed in an infant or young child who suddenly has very red eyes. To the ophthalmologist, the cornea looks like frosted glass. This disorder may recur several times per year and disappear when affected individuals are in their 20s or 30s.
Stromal dystrophies
The primary dystrophies found in the stromal layer are granular dystrophy, lattice dystrophy, and macular dystrophy. Granular dystrophy is so named because of the small opaque areas caused by deposits of hyaline, a substance that accumulates as cells deteriorate. Lattice dystrophy is caused by deposits of amyloid, the same substance that accumulates in the brain in people with Alzheimer disease. Both granular dystrophy and lattice dystrophy have been identified in family members in Avellino, Italy, and these dystrophies are sometimes grouped together and called Avellino corneal dystrophy. Lattice and granular dystrophies can cause severe eye pain. With lattice dystrophy, by about age 40, an affected person's vision can be very obscured and a corneal transplant is required.
Endothelial dystrophies
Fuchs' dystrophy is the most common of the endothelial dystrophies and is inherited as an autosomal dominant trait. It is characterized by blurred vision, hypersensitivity to light (photophobia), and two to eight acute inflammatory attacks per year. It may also cause ulceration and erosion of the cornea. Fuchs' can cause deterioration of endothelial cells and result in corneal guttata, which are thickenings or leakages from the Descemet's membrane of the cornea. These guttata eventually cause edema (excessive fluid) to leak into the stromal or epithelial areas.
Posterior polymorphous dystrophy (PPD), an autosomal dominant disease, also causes edema, although it affects a larger area than Fuchs' dystrophy. It usually does not cause vision impairment.
Congenital hereditary endothelial dystrophy (CHED) comprises two types. The autosomal dominant
form is CHED 1 and the recessive form is CHED 2. CHED 1 can occur in early childhood and may also cause hearing loss. The key symptoms of CHED 1 are sensitivity to light and excessive tearing. CHED 2 is present at birth and is more severe than CHED 1. In both CHED 1 and 2, the cornea presents with a milky haze or the appearance of ground glass.
Macular dystrophy is inherited as an autosomal recessive trait. It can present as early as age three and up to about age nine and is very debilitating. This disorder is caused by deposits of keratin sulfate (sulfur-containing fibrous proteins) and becomes increasingly painful. The child will have a feeling of something in the eye and also experience photophobia (sensitivity to light).
Diagnosis
Corneal dystrophy may be identified by an optometrist and diagnosed by an ophthalmologist. The findings determine the existence and type of corneal dystrophy. The presence, size, and shape of any opaque material in the eyes are considered.
The affected cornea of a person with lattice dystrophy will have a ground glass appearance, while granular deposits indicate granular dystrophy. The examination can also reveal the presence of amyloid deposits, which are typical of individuals with lattice dystrophy.
Treatment and management
Treatment depends on the severity of the disease. If the affected person is in acute pain, treatment with eye drops, antibiotics, and other solutions is necessary. Some doctors advise affected people with eye edema to use a hair dryer at arm's length to dry some of the edema. Soft contact lenses may also help. Individuals with increasingly severe vision problems may need a corneal transplant.
For other forms of corneal dystrophy, affected people may need artificial tears and other medications. Some individuals may need laser treatment, such as phototherapeutic keratectomy (PK), which is the removal of part of the corneal stroma, or they may need a corneal transplant.
Prognosis
With most forms of corneal dystrophy, the disease progresses as the affected person ages. The severity of the conditions varies and a particular form of the disease may
cause few or no problems or may also cause severe visual difficulties requiring surgery. Cases must be evaluated individually.
PERIODICALS
Akimune, Chika, et al. "Corneal Guttata Associated with the Corneal Dystrophy Resulting from a Big-h3 R124H Mutation." British Journal of Ophthalmology 84 (January 2000).
Bass, Sherry J. "Unraveling the Genetic Mysteries of the Corneal Dystrophies." Review of Optometry 138 (January 15, 2001).
Kabat, Alan G., and Joseph W. Sowka. "How to Detect and Deal with Dystrophies and Degenerations." Review of Optometry 136 (November 1999).
Korvatska, E., et al. "Mutation Hot Spots in 5q31-Linked Corneal Dystrophies." American Journal of Human Genetics 62 (1998).
National Eye Institute. "Fact Sheet: The Cornea and Corneal Disease." April 2000.
ORGANIZATIONS
Eye Bank Association of America. 1015 18th St. NW, Suite 1010, Washington, DC 20036. (202) 775-4999. <http://www.restoresight.org/>.
National Association for Visually Handicapped. 22 West 21st Street, New York, NY 10010. (212) 889-3141. <http://www.navh.org>.
National Eye Institute. 31 Center Dr., Bldg. 31, Rm 6A32, MSC 2510, Bethesda, MD 20892-2510. (301) 496-5248. 2020@nei.nih.gov. <http://www.nei.nih.gov>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
