BASICS

DESCRIPTION

• 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.

EPIDEMIOLOGY

• 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

Incidence

Unknown.

Prevalence

4% of the population >40 years old.

RISK FACTORS

• Patient age

• Raised intraocular pressure

• Ocular inflammation

Genetics

• 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

• Gene:

– Early-onset variant FECD collagen type VIII, Alpha 2-COL8A2

PATHOPHYSIOLOGY

• 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

ETIOLOGY

• 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

• Cataracts

• Recurrent erosions from bullae

• Open-angle glaucoma

• Angle-closure glaucoma

• Keratoconus (rare)

DIAGNOSIS

HISTORY

• 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

PHYSICAL EXAM

• 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

Lab

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

Diagnostic Procedures/Other

Confocal microscopy can identify and diagnose endothelial cell findings in patients with severe corneal edema that precludes slit-lamp examination.

Pathological Findings

• 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

DIFFERENTIAL DIAGNOSIS

• 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:

– Trauma

– Intraocular inflammation

– Infection

– Toxins

TREATMENT

MEDICATION

First Line

• 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.

Second Line

• If pressure is elevated, add antiglaucoma medications (see Glaucoma section).

ADDITIONAL TREATMENT

General Measures

• 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

SURGERY/OTHER PROCEDURES

• 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).

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• 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

Patient Monitoring

• Continued follow-up with complete ophthalmic examination and slit-lamp examination

• Ultrasound pachymetry and specular microscopy as required

PATIENT EDUCATION

• 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)

PROGNOSIS

• 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.

• DSEK and DMEK are relatively new procedures. Results for DSEK at 12 months are excellent (98% >20/40) (3–4).

COMPLICATIONS

• Painful bullous keratopathy

• Corneal ulceration with infectious keratitis

• Post keratoplasty:

– Rejection

– Graft failure

– Glaucoma

– Astigmatism

– Anisometropia

– Corneal ulcer

– Wound dehiscence

– Uveitis

– Epithelial downgrowth

– Retinal detachment

– Endophthalmitis

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