Description

• Fuchs (pronounced Fooks) endothelial corneal dystrophy is a bilateral, progressive, noninflammatory disease of the eye characterized by endothelial dysfunction, leading to corneal edema and vision loss.
• Keratoplasty (full- or partial-thickness corneal transplant) is the definitive management step for restoration of vision.

Epidemiology

• Typically presents in the 5th and 6th decades, with rare early-onset Fuchs dystrophy in the 1st decade of life
• The leading indication for corneal transplant in the United States
• Accounts for >15,000 cases of keratoplasty in the most recent year (1)

Incidence
Unknown

Prevalence

• Women appear more susceptible than men, 3 to 4:1.
• 5% of the U.S. population >40 years old (2)

Etiology and Pathophysiology

• The cornea provides 74% of the refractive power of the human eye and is composed of five layers: epithelium, Bowman layer, stroma, Descemet membrane, and endothelium.
• The endothelium provides vital barrier and ion transport functions, enabled by Na⁺/K⁺ ATPase pumps, which regulate corneal hydration and transparency.
• Attrition of endothelial cells accompanies normal aging: Endothelial cell density averages 2,400 cells/mm² in adults, contrasted with 6,000 cells/mm² in infants.
• Endothelial cell density is also adversely impacted by intraocular insults, notably cataract surgery and elevated intraocular pressure (IOP).
• In Fuchs dystrophy, endothelial stress manifests as endothelial cell morphologic changes and decreased cellular density, abnormal deposition of collagen and extracellular matrix in Descemet membrane, resulting in progressive stromal edema.
• Changes in Descemet membrane can be visualized microscopically as thickening and characteristic anvil-shaped refractive granules known as guttae (Latin: drops) which are first visible in the central cornea and spread progressively toward the periphery.
• As endothelial barrier and ion transport functions are increasingly overwhelmed, endothelial cell attrition accelerates and the central cornea becomes grossly thickened.
• Epithelial edema develops late in the disease course, associated with painful epithelial bullae, subepithelial fibrosis, and superficial corneal neovascularization.

Genetics

• Most commonly presents without known inheritance (category 3)
• Late-onset familial and sporadic cases less commonly are linked to genetic loci (category 2).
  • A strong correlation between clinical severity of known disease and expansion of CTG repeats has been reported on 18q21.2, at the locus coding for the widely expressed transcription factor TCF4, but its role in pathogenesis remains unclear (2)[B].
  • Several chromosomal loci on 1, 5, 7, 9, 13, 15, 17, and X chromosomes have been implicated, with both autosomal dominant and complex inheritance patterns (3).
• Early-onset variant genetic locus (category 1)
  • 1p34.3–p32, associated with collagen type VIII α₂ (COL8A2) gene

Risk Factors

• Age >50 years
• Female gender
• Smoking
• Diabetes
• Family history of Fuchs dystrophy

Commonly Associated Conditions

• Bullous keratopathy
• Angle-closure glaucoma
• Open-angle glaucoma
• Cataracts