Fuchs' dystrophy

Fuchs' dystrophy
Classification and external resources
Fuchs' corneal dystrophy. Light microscopic appearance of the cornea showing numerous excrescences (guttae) on the posterior surface of Descemet's membrane and the presence of cysts in the corneal epithelium beneath ectopically placed intraepithelial basement membrane. Periodic acid-Schiff stain. From a review by Klintworth, 2009.
ICD-10	H18.5
ICD-9	371.57
OMIM	136800 610158
DiseasesDB	31163
MedlinePlus	007295
eMedicine	article/1193591
MeSH	D005642

Fuchs' dystrophy (pronounced fooks-DIS-trə-fe) also known as Fuchs' endothelial dystrophy, is a slowly progressing corneal dystrophy 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 ophthalmologist Ernst Fuchs (1851–1930), after whom it is named.

Epidemiology

Fuchs' dystrophy rarely affects individuals under 50 years of age.

Etiology

Fuchs’ endothelial dystrophy (FED) is a degenerative disease of the corneal endothelium with accumulation of focal outgrowths called guttae (drops) and thickening of Descemet’s membrane, leading to corneal edema and loss of vision. 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), which results in 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 fewer 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 the early-onset FED.

Genes include:

Type	OMIM	Gene	Locus
FECD1	136800	COL8A2	1p34.3-p32.3
FECD4	610206	SLC4A11	20p13-p12
FECD6	189909	ZEB1	10p11.2

Signs and symptoms

At first, a person with Fuchs' dystrophy will awaken with blurred vision 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 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. 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.

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).

Since 1998, new surgical modalities in the treatment of FED have been developed, initially by G. Melles et al. in The Netherlands. These procedures, called posterior lamellar keratoplasty or endothelial keratoplasty, have been popularized as deep lamellar endothelial keratoplasty (DLEK) and Descemet’s stripping with endothelial keratoplasty (DSEK). DLEK and DSEK avoid some of the surgical complications of PKP such as wound dehiscence and high postoperative astigmatism. Since 2004, DSEK has become the dominant procedure for patients with corneal disease restricted to the endothelium. It can be technically easier for the surgeon compared to DLEK, and may provide superior visual results. With DSEK, patients must remain supine (face up positioning) for 24 or more hours following the procedure while the transplanted tissue adheres to the overlying cornea.

Improved surgical instrumentation for DSEK, such as DSEK graft injectors, and technical improvements in the surgical technique have facilitated reduced complications and the potential to perform DSEK through very small (3mm) sutureless incision.

Recently, endothelial keratoplasty has been further refined to Descemet Membrane Endothelial Keratoplasty (DMEK), in which only a donor Descemet membrane and its endothelium is transplanted. With DMEK, 90% of cases achieve a best spectacle corrected visual acuity 20/40 or better, and 60% of cases 20/25 or better within 1–3 months, although complications such as graft failure and detachment remain challenges for the patient and surgeon.

More speculative future directions in the treatment of FED include in vitro expansion of human corneal endothelial cells for transplantation, artificial corneas (keratoprosthesis) and genetic modification.

See also

• Fuchs heterochromic iridocyclitis (a disease of the iris)
• Ocular straylight

External links

Medical institutes

• Facts About the Cornea and Corneal Disease - The National Eye Institute (United States)
• Descemet Membrane Endothelial Keratoplasty
• Summary of scientific literature

Support groups

• FuchsSupport
• Fuchsfriends UK
• The Corneal Dystrophy Foundation
• Fuchs' Dystrophy Science - Open Discussion