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.[1]
ICD-10	H18.5
ICD-9	371.57
OMIM	136800 610158
DiseasesDB	31163
eMedicine	article/1193591
MeSH	D005642

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), after whom it is named.

Etiology

Fuchs’ endothelial dystrophy (FED) is a degenerative 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. 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.^[2]

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 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).

Since 1998, new surgical modalities in the treatment of FED have been developed by 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 the surgical complications of PKP such as wound dehiscence and infections and high postoperative astigmatism. Since 2004, DSEK has become the dominant procedure because it is technically much easier for the surgeon compared to DLEK or PKP. Improved surgical instrumentation for DSEK, such as a DSEK graft injector will become available shortly (2008). This could allow faster recovery for patients because of the ability to perform DSEK through very small (3 mm) sutureless incisions.

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.

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

See also

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

References

1. ^ Klintworth GK (2009). "Corneal dystrophies". Orphanet J Rare Dis 4: 7. doi:10.1186/1750-1172-4-7. PMC 2695576. PMID 19236704. http://www.ojrd.com/content/4//7. 
2. ^ Gottsch JD, Sundin OH, Liu SH, et al. (June 2005). "Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of fuchs corneal dystrophy". Invest. Ophthalmol. Vis. Sci. 46 (6): 1934–9. doi:10.1167/iovs.04-0937. PMID 15914606. http://www.iovs.org/cgi/pmidlookup?view=long&pmid=15914606. 

External links

• Facts About the Cornea and Corneal Disease The National Eye Institute (NEI)
• Descemet Membrane Endothelial Keratoplasty
• Summary of scientific literature
• The Corneal Dystrophy Foundation