• Fuchs’ corneal dystrophy is a progressive, bilateral, noninflammatory condition characterized by the development of focal excrescences of Descemet’s membrane with resultant guttae, loss of endothelial cells, and resultant stromal edema. See Figures 1–3.
• The loss of the ion transport system and barrier function of the compromised endothelial cell layer leads to progressive stromal edema and eventual formation of epithelial bullae.
• Symptoms include glare and blurred vision worse upon awakening. This may progress to pain, photophobia and epiphora from erosions and rupture of the epithelial bullae.
• Predominant gge: 5th and 6th decades (exception= Early-onset variant Fuchs’ endothelial corneal dystrophy in first decade [rare])
• Predominant sex: Females > Males, 3.5:1
4% of the population >40 years old.
• Patient age
• Raised intraocular pressure
• Ocular inflammation
• Autosomal dominant inheritance, often with incomplete penetrance and asymmetric presentation (1)
• Genetic locus:
– Fuchs endothelial corneal dystrophy (FECD) 13pTel-13q12.13, 15q, 18q21.2-q21.32
– Early-onset variant FECD 1p34.3-p32
– Early-onset variant FECD collagen type VIII, Alpha 2-COL8A2
• Primary dysfunction of the endothelial cell layer causes abnormal production of Descemet’s membrane.
• Descemet’s membrane becomes 2–3 times thicker with guttae excrescences of excess collagen visible with PAS and H&E staining.
• Reduction in the number of endothelial cells, followed by variations in size (polymegathism) and shape (polymorphism) are characteristic.
• The compromised endothelial cell layer leads to progressive stromal edema and eventually formation of epithelial bullae and corneal erosions.
• In end stage disease subepithelial fibrosis, anterior basement membrane changes, ± superficial neovascularization of the cornea can occur
• Endothelial cell loss increases with age
• Average endothelial cell density = 6000 cells/mm2 in infants and 2400 cells/mm2 in adults
• Significant reduction of endothelial cells after intraocular surgery—especially cataract surgery. Fuchs’ patients already have compromised endothelial cells.
• Loss of the endothelial layer’s barrier function and Na+/K+-ATPase pump function leads to increased permeability of the endothelial layer producing stromal and epithelial edema.
COMMONLY ASSOCIATED CONDITIONS
• Recurrent erosions from bullae
• Open-angle glaucoma
• Angle-closure glaucoma
• Keratoconus (rare)
• Any previous cataract surgery
• Any previous ocular surgery
• Glare, blurred vision worse upon awakening
• Pain, photophobia, and epiphora from erosions and bullae
• Past history of glaucoma or uveitis
• Full ophthalmic examination including measurement of intraocular pressure and dilated fundus examination
• B-scan ultrasound to rule out posterior segment pathology if unable to visualize secondary to corneal or lenticular changes
• Slit-lamp examination shows:
– In early stages—central corneal guttae on direct illumination and retroillumination
– Later stages—guttae spread peripherally, with a beaten metal endothelial appearance secondary to increased pigmentation of the guttae, thickening of Descemet’s membrane
– Corneal edema is initially in the posterior stroma and also posterior to Bowman’s membrane seen best with sclerotic scatter.
– Worsening edema leads to folds in Descemet’s membrane, microcystic epithelial edema that coalesces and forms bullae.
– Peripheral superficial corneal neovascularization occurs in end stage Fuchs’ as well as bullae formation.
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Slit-lamp examination (as mentioned in previous section)
• Ultrasound pachymetry to measure central corneal thickness
• Specular microscopy to measure endothelial cell counts, guttae, and levels of endothelial cell polymegathism and polymorphism
Follow-up & special considerations
• Slit-lamp examination
• Ultrasound pachymetry
• Specular microscopy
• Significant clinical findings require treatment using hypertonic saline topical drop and/or ointment, or surgery
• Evaluation of cataract if present
Confocal microscopy can identify and diagnose endothelial cell findings in patients with severe corneal edema that precludes slit-lamp examination.
• Diffusely thickened Descemet’s membrane
• Anvil-shaped excrescences of basement membrane (guttae) within Descemet’s membrane
• Paucity of endothelial cells
• Varying degrees of subepithelial fibrosis and anterior basement membrane changes
• Bullous keratopathy ± neovascularization of the epithelium may be present
• Pseudophakic/aphakic corneal edema
• Posterior polymorphous dystrophy
• Congenital hereditary endothelial dystrophy
• Macular dystrophy
• Interstitial keratitis
• Central herpetic disciform keratitis
• Chandler’s syndrome (iridocorneal endothelial syndrome)
• Corneal pseudoguttae from the following:
– Intraocular inflammation
• Topical hypertonic saline (5%) drops (1 drop q.i.d.) and ointment (q.h.s. or if preferable q.i.d. instead of drops). No contraindications.
• If pressure is elevated, add antiglaucoma medications (see Glaucoma section).
• Initial treatment is reduction of corneal edema and pain relief.
• If epithelial bullae rupture, can manage with a therapeutic bandage contact lens. Risk for corneal ulcer is increased.
• Use a hair dryer on the eyes to dehydrate the cornea.
• Surgical intervention is required for visual rehabilitation when there is significant reduction of vision that fails all medical therapy.
Issues for Referral
• Worsening vision
• Corneal ulcer
• Full-thickness penetrating keratoplasty (PKP) is required for compliant patients with advanced Fuchs’ dystrophy who have central anterior scarring, anterior basement membrane changes, or subepithelial fibrosis.
• In patients without central anterior stromal scarring or subepithelial fibrosis, an endothelial keratoplasty (EK) may be required, either
– Descemet’s stripping endothelial keratoplasty (DSEK/DSAEK)
– Descemet’s membrane endothelial keratoplasty (DMEK)—relatively new procedure
• Compared with PKP, EK is preferred as recovery time is less, less induced astigmatism, less chance for wound dehiscence.
• Patients with Fuchs’ dystrophy and visually significant cataract may benefit from cataract surgery alone, or combined cataract surgery with keratoplasty (PKP or EK as in guidelines earlier.).
– The current guidelines recommend a combined cataract surgery with keratoplasty be considered when the endothelial cell count is <1000/mm2 or central corneal thickness is >650 mm, although other clinical factors should be considered by the surgeon (2).
• Depends on severity of disease
• Typically follow-up every 3–12 months
• In cases with ruptured bullae and epithelial defects, follow-up as in corneal abrasions
• Continued follow-up with complete ophthalmic examination and slit-lamp examination
• Ultrasound pachymetry and specular microscopy as required
• This is usually a slowly progressive condition
• Primarily autosomal dominant
• Hypertonic saline treatment can halt progression in most cases
• Hypertonic saline topical drops cause stinging and patients should be reassured that this is normal to maximize compliance
• Hypertonic saline topical ointment does not cause stinging, but causes blur. It is ideally used at bedtime or in eyes that already have significantly reduced vision
• If vision is worse in the morning it is usually attributed to Fuchs’ dystrophy as corneal edema increases while sleeping
• Patients with Fuchs’ dystrophy undergoing cataract surgery should be warned that there is a higher probability of postoperative corneal edema that may require corneal transplantation (keratoplasty)
• Keratoplasty by itself will accelerate cataract formation so if the patient is still phakic, cataract extraction with keratoplasty is usually performed (depending on surgeon’s discretion)
• Fuchs’ dystrophy is a progressive disease that worsens over time; however, the course is variable.
• After any intraocular surgery, endothelial cell loss occurs.
• Prognosis after PKP is good with most patients (>80%) with clear corneal transplants from 2 to 5 years after surgery, but long-term prognosis is not as good.
• Painful bullous keratopathy
• Corneal ulceration with infectious keratitis
• Post keratoplasty:
– Graft failure
– Corneal ulcer
– Wound dehiscence
– Epithelial downgrowth
– Retinal detachment
1. Weiss JS, Moller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea 2008;27Suppl.2:S26–S28.
2. Eghrari AO, Daoud YJ, Gottsch JD. Cataract surgery in Fuchs’ corneal dystrophy. Curr Opin Ophthalmol 2010;21:15–19.
3. Lee WB, Jacobs DS, Musch DC, et al. Descemet’s stripping endothelial keratoplasty: Safety and outcomes: A report by the American Academy of Ophthalmology. Ophthalmology 2009;116:1818–1830.
4. Terry MA, Shamie N, Chen ES, et al. Endothelial keratoplasty for Fuchs’ dystrophy with cataract: Complications and clinical results with the new triple procedure. Ophthalmology 2009;116:631–639.