Fuchs Endothelial Dystrophy

Fuchs endothelial corneal dystrophy is a bilateral, progressive degeneration of corneal endothelium with excrescences of Descemet membrane (guttae), accelerated endothelial cell loss, and eventual corneal oedema from failure of the endothelial pump.

• It is the commonest corneal dystrophy needing transplantation, affecting about 4 percent of adults over 40 years, more in women (about 2 to 3 times).
• Genetics: autosomal dominant with variable penetrance; a trinucleotide repeat expansion in TCF4 (more than 50 repeats) is present in about 70 percent in European populations, and mutations in COL8A2 occur in early onset forms.
• Associations: smoking, diabetes, and ultraviolet exposure as modifiers; cataract surgery can unmask oedema in a cornea with guttae (pseudophakic bullous keratopathy).

• Guttae begin centrally in the fifth decade and may remain asymptomatic for years.
• Stage 1: guttae without oedema.
• Stage 2: stromal and epithelial oedema with morning blurring that clears during the day (evaporation of tear film and open eyes), glare, haloes, and cloudy vision.
• Stage 3: epithelial bullae that rupture causing pain and tearing, subepithelial fibrosis, and permanent visual loss.
• Stage 4: dense subepithelial scarring and vascularisation, with reduced pain.

• Slit lamp: beaten bronze appearance of the endothelium by specular reflection, guttae, stromal oedema, folds in Descemet, epithelial microcysts and bullae.
• Specular microscopy: endothelial cell density (often below 1000 cells/mm2 in symptomatic cases) with pleomorphism, and dark guttae; normal adult density is 2000 to 3000.
• Pachymetry: central corneal thickness above 600 micrometres suggests oedema, and values above 640 micrometres suggest decompensation; corneal tomography shows posterior surface irregularity and loss of regular isopachs (earliest sign of oedema).
• Anterior segment OCT shows hyperreflective guttae and stromal and epithelial thickening.
• Examination for angle closure and glaucoma.
• Genetic testing is optional.

• Early disease: observation. Preoperative counselling before cataract surgery in patients with guttae, with attention to endothelial protection (dispersive viscoelastic, minimal phaco energy).
• Medical management of oedema:
  • Hypertonic saline 5 percent drops three to four times daily and ointment at night.
  • Warm dry air from a hairdryer held at arm's length for a few minutes in the morning.
  • Lubricants and control of intraocular pressure (timolol 0.5 percent twice daily; avoid prostaglandin analogues if inflamed), and bandage contact lens for bullae pain.
  • Topical NSAIDs or cycloplegia for bullous pain.
• Surgery when vision is impaired and daily function limited:
  • Descemet membrane endothelial keratoplasty (DMEK) is the preferred operation: replace the recipient Descemet membrane and endothelium with a donor graft of Descemet membrane and endothelium, using an air or 20 percent sulphur hexafluoride gas bubble to oppose the graft, and patient positioning supine for 1 to 2 days. Visual recovery is the fastest (best acuity 20/25 or better in most), and rejection rates are lowest (under 2 percent). Rebubbling is needed in about 20 to 30 percent of cases for graft detachment.
  • Descemet stripping automated endothelial keratoplasty (DSAEK) uses a thicker donor lenticule that includes some stroma; used when DMEK is unsuitable (anterior chamber abnormalities, vitrectomised eyes, glaucoma tube).
  • Penetrating keratoplasty only for extensive scarring.
  • Combined cataract surgery and endothelial keratoplasty when cataract is visually significant and oedema is present; staged cataract surgery first if the cornea is only mildly oedematous.
  • Selected central cases: Descemet stripping only (no graft) with topical ripasudil 0.4 percent (a rho kinase inhibitor, or netarsudil 0.02 percent) 1 drop four times daily for 2 to 8 weeks to promote endothelial migration, in eyes with a peripheral reserve of healthy endothelium.
• Postoperative regimen (DMEK): prednisolone acetate 1 percent four times daily with slow taper over 6 to 12 months, then low strength steroid (fluorometholone 0.1 percent once daily) long term to reduce rejection; antibiotic drops for 1 to 2 weeks; cycloplegic for 1 week; check pressure frequently.
• Follow up: day 1, week 1, month 1, 3, 6, and annually; rejection presents with redness, photophobia, and blurred vision and is treated with intensified topical corticosteroid (prednisolone 1 percent hourly) and a short course of oral prednisolone.
• Complications: graft detachment, primary graft failure, rejection, glaucoma, infection, and cystoid macular oedema.