Fuchs' dystrophy

Fuchs' dystrophy
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.
Classification and external resources
Specialty
ICD-10	H18.5
ICD-9-CM	371.57
OMIM	136800 610158
DiseasesDB	31163
MedlinePlus	007295
eMedicine	article/1193591
Patient UK	Fuchs' dystrophy
MeSH	D005642

Fuchs' dystrophy (pronounced fooks-DIS-trə-fe), also known as Fuchs' corneal endothelial dystrophy or FCED, 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. In 1910, Fuchs first reported 13 cases of central corneal clouding, loss of corneal sensation and the formation of epithelial bullae, which he labeled ‘dystrophia epithelialis corneae’. It was characterized by late onset, slow progression, decreased visual acuity in the morning, lack of inflammation, diffuse corneal opacity, intense centrally, and roughened epithelium with vesicle-like features. A shift to the understanding of Fuchs’ corneal endothelial dystrophy (FCED) as primarily a disease of the corneal endothelium resulted after a number of observations in the 1920s. Crystal-like features of the endothelium were noted by Kraupa in 1920, who suggested that the epithelial changes were dependent on the endothelium. Using a slit lamp, Vogt described the excrescences associated with FCD as drop-like in appearance in 1921. In 1924, Graves then provided an extremely detailed explanation of the endothelial elevations visible with slit-lamp biomicroscopy. A patient with unilateral epithelial dystrophy and bilateral endothelial changes was described by the Friedenwalds in 1925; subsequent involvement of the second eye led them to emphasize that endothelial changes preceded epithelial changes. As only a subset of patients with endothelial changes proceeded to epithelial involvement, Graves stated on 19 October 1925 to the New York Academy of Medicine that “Fuchs’ epithelial dystrophy may be a very late sequel to severer cases of the deeper affection”.

Epidemiology

Few studies have examined the prevalence of FCED on a large scale. First assessed in a clinical setting, Fuchs himself estimated the occurrence of dystrophia epithelialis corneae to be one in every 2000 patients; a rate that is likely reflective of those who progress to advanced disease. Cross-sectional studies suggest a relatively higher prevalence of disease in European countries relative to other areas of the world. Fuchs' dystrophy rarely affects individuals under 50 years of age.

Etiology

Fuchs’ corneal endothelial dystrophy (FCED) 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 FCED 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.

FCED 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 FCED.

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 symptomatic Fuchs' dystrophy will 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.

Treatment

Medical 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.

Since 1998, new surgical modalities in the treatment of FCED have been developed, initially by G. Melles et al. in The Netherlands. These procedures, called posterior lamellar keratoplasty or endothelial keratoplasty, were initially 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. DMEK is available in the United Kingdom at the Calderdale and Huddersfield Hospitals.

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.

A greater understanding of FED pathophysiology may assist in the future with the development of treatments to prevent progression of disease. Although much progress has been made in the research and treatment of FED, many questions remain to be answered. The exact causes of illness, the prediction of disease progression and delivery of an accurate prognosis, methods of prevention and effective nonsurgical treatment are all the subject of inquiries that necessitate an answer. Increased attention must be given to research that can address the most basic questions of how disease develops: what is the biomolecular pathway implicated in disease, and what genetic or environmental factors contribute to its progression? In addition to shaping our understanding of FED, identification of these factors would be essential for the prevention and management of this condition.

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