Lecture 29 - Corneal Dystrophies

What are corneal dystrophies?

A group of bilateral, genetic, noninfectious, noninflammatory, typically symmetrical corneal diseases causing accumulation of deposits within corneal layers

What is the usual origin of corneal dystrophies?

Endogenous with little or no relationship to environmental or systemic factors

When do corneal dystrophies usually begin?

Early in life, although they often do not become clinically significant until later in life

Where in the cornea do most corneal dystrophies occur?

Central cornea

How are corneal dystrophies broadly categorized?

By the corneal layer or depth affected

Which corneal layers are involved in anterior or superficial corneal dystrophies?

Epithelium and Bowman's layer

Which corneal layer is involved in stromal corneal dystrophies?

Stroma

Which corneal layers are involved in posterior corneal dystrophies?

Descemet's membrane and endothelium

What are the alternate names for epithelial basement membrane dystrophy (EBMD)?

Anterior basement membrane dystrophy, Cogan's microcystic dystrophy, and map-dot-fingerprint dystrophy

What is the most common anterior corneal disorder?

Epithelial basement membrane dystrophy (EBMD)

Why is EBMD sometimes considered a degeneration instead of a dystrophy?

Because it is extremely common and only rarely autosomal dominant

What is the primary pathophysiology of EBMD?

Abnormal epithelial turnover and maturation causing thickened basement membrane and aberrant fibrillary projections into the epithelium

How does EBMD lead to recurrent corneal erosions?

Impaired epithelial adhesion due to structural abnormalities and abnormal hemidesmosome attachment leads to intermittent epithelial sloughing

Why do maps, dots, cysts, and fingerprint patterns form in EBMD?

Trapped epithelial cells create abnormal epithelial appearances

At what age does EBMD typically present?

Usually 20-40 years old, though prominent lesions may not appear until the 50s or 60s

Is EBMD unilateral or bilateral?

Bilateral, but may be asymmetric

Is EBMD hereditary?

It may have a variable hereditary component

Are patients with EBMD usually symptomatic?

No, most are asymptomatic

What visual symptoms can occur in EBMD?

Blurred vision, fluctuating vision, glare, distortion, and monocular diplopia (ghosting)

What ocular discomfort symptoms can occur in EBMD?

Photophobia and foreign body sensation

What painful complication may occur in advanced EBMD?

Recurrent corneal erosions, either spontaneous or following trauma

What are the map lesions seen in EBMD?

Intraepithelial gray patches

What are the dot lesions seen in EBMD?

Creamy white round or comma-shaped microcysts/opacities

What are fingerprint lesions in EBMD?

Clusters of irregular concentric lines resembling ripples on a pond

How are maps and dots best visualized in EBMD?

With fluorescein staining

How are fingerprint lesions best visualized in EBMD?

With retroillumination

What causes negative staining in EBMD?

Raised epithelial lesions

What are the findings of recurrent corneal erosion in EBMD?

Localized loose epithelium and distinct epithelial defects

What percentage of EBMD patients develop recurrent corneal erosions?

Approximately 10%

What percentage of recurrent corneal erosions are caused by EBMD?

Approximately 30%

How is asymptomatic EBMD managed?

Observation and monitoring

How are irritation and dry-eye symptoms managed in EBMD?

Preservative-free artificial tears and ointment at bedtime

What treatments can be used for recurrent corneal erosions in EBMD?

PFATs, hypertonic saline drops or ointment, pressure patching, topical corticosteroids, and oral doxycycline

What advanced therapies can be used for EBMD-related recurrent corneal erosions?

Bandage contact lenses and amniotic membranes

What surgical procedures can treat EBMD-related recurrent corneal erosions?

Epithelial debridement, anterior stromal puncture, diamond burr polishing, and phototherapeutic keratectomy (PTK)

Why are specialty rigid gas permeable lenses used in EBMD?

To provide optimal vision over irregular corneal surfaces

What is PTK in the treatment of EBMD?

Excimer laser removal of faulty epithelium and basement membrane

What is another name for Meesmann corneal dystrophy?

Juvenile hereditary epithelial dystrophy

What causes Meesmann corneal dystrophy?

Thickened epithelial basement membrane with hundreds to thousands of tiny intraepithelial vesicles filled with cellular debris

How is Meesmann corneal dystrophy inherited?

Autosomal dominant

When does Meesmann corneal dystrophy present?

In the first few years of life

When do symptoms of Meesmann corneal dystrophy usually appear?

Typically not until middle age

What symptoms occur in Meesmann corneal dystrophy?

Glare, photophobia, blurry vision, dryness, foreign body sensation, and recurrent corneal erosions in severe cases

What is the hallmark sign of Meesmann corneal dystrophy on retroillumination?

Countless tiny translucent epithelial cysts extending to the limbus

How do Meesmann dystrophy lesions appear with direct illumination?

Gray or clear lesions

How is Meesmann corneal dystrophy managed?

Observation if asymptomatic, lubrication, sunglasses, bandage contact lenses, superficial keratectomy, and management of recurrent corneal erosions

What causes Reis-Bücklers corneal dystrophy?

Hyaline-like deposits accumulate in Bowman's membrane and anterior stroma causing damage and scarring

How is Reis-Bücklers dystrophy inherited?

Autosomal dominant

Is Reis-Bücklers dystrophy common or rare?

Rare

When does Reis-Bücklers dystrophy present?

During the first few years of life

What symptoms are characteristic of Reis-Bücklers dystrophy?

Severe recurrent corneal erosions beginning early in life and reduced BCVA by the second or third decade

What slit-lamp findings are seen in Reis-Bücklers dystrophy?

Irregular gray-white reticular subepithelial opacities in Bowman's layer and anterior stroma that progress deeper into the stroma

How is mild Reis-Bücklers dystrophy managed?

Lubrication

How is advanced Reis-Bücklers dystrophy managed?

Bandage contact lenses, superficial keratectomy, PTK, lamellar keratoplasty, or penetrating keratoplasty

Can Reis-Bücklers dystrophy recur after treatment?

Yes, even within donor corneal grafts

What causes Thiel-Behnke corneal dystrophy?

Curly collagen fibrils accumulating in Bowman's layer and anterior stroma

How can Thiel-Behnke dystrophy be distinguished from Reis-Bücklers dystrophy?

Transmission electron microscopy is required to differentiate them

What are the characteristic lesions of Thiel-Behnke dystrophy?

Honeycomb ring-shaped subepithelial opacities with multiple flecks in a reticular pattern

Can Thiel-Behnke dystrophy extend into deeper stroma?

Yes

What gene mutation is associated with lattice dystrophy?

TGFBI gene mutation on chromosome 5q31

Which dystrophies share the TGFBI mutation?

Lattice, Reis-Bücklers, Thiel-Behnke, granular, and Avellino dystrophies

What material accumulates in lattice dystrophy?

Amyloid deposits between the epithelial basement membrane, Bowman's layer, and within the stroma

How does amyloid stain in lattice dystrophy?

Pink with Congo red stain

How do classic lattice dystrophy lesions appear?

Fine branching refractile lines in the anterior and mid stroma resembling cracked glass

Where do lattice dystrophy lesions occur?

Centrally and usually spare the peripheral cornea

When does lattice dystrophy begin?

First decade of life, though symptoms occur later

What symptoms occur in lattice dystrophy?

Progressive blurred vision, pain from recurrent corneal erosions, irritation, and progressive corneal hypesthesia

What happens in advanced lattice dystrophy?

Diffuse anterior stromal haze, fibrosis, scarring, and cloudy vision develop

How is lattice dystrophy managed?

Lubrication, treatment of recurrent corneal erosions, and surgical treatments similar to Reis-Bücklers dystrophy

How is granular dystrophy inherited?

Autosomal dominant with variable penetrance

What gene is associated with granular dystrophy?

TGFBI mutation on chromosome 5q31

What accumulates in granular dystrophy type I?

Hyaline-like deposits between the epithelial basement membrane, Bowman's layer, and anterior stroma

How do the deposits of granular dystrophy type I stain?

Red with Masson's trichrome stain

When do symptoms of granular dystrophy usually occur?

Third to fourth decade despite childhood onset

What are the characteristic opacities of granular dystrophy type I?

Multiple discrete white-to-gray crumb-like deposits resembling breadcrumbs or sugar granules separated by clear stroma

How large are the deposits in granular dystrophy type I?

Approximately 50-500 µm and variable in shape

What is another name for granular dystrophy type II?

Avellino dystrophy or combined granular-lattice dystrophy

What accumulates in Avellino dystrophy?

Both hyaline-like and amyloid deposits

How do Avellino dystrophy deposits stain?

Positive with both Masson's trichrome and Congo red stains

What are the characteristic findings in Avellino dystrophy?

Crumb-like opacities combined with deeper stromal refractile linear lattice lesions

How are granular dystrophies managed?

Similar to lattice dystrophy, although PTK is often less successful and recurrence may occur in corneal grafts

What contact lens may provide optimal vision in granular dystrophy?

Scleral RGP lens

How is macular dystrophy inherited?

Autosomal recessive

What accumulates in macular dystrophy?

Glycosaminoglycans within the epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium

How do deposits in macular dystrophy stain?

Blue with Alcian blue stain

How does macular dystrophy type I differ from type II?

Type I presents in childhood and lacks keratan sulfate, whereas type II presents in the second decade and contains keratan sulfate

What symptoms occur in macular dystrophy?

Glare, blurred vision by the third decade, and recurrent corneal erosion potential

What are the slit-lamp findings in macular dystrophy?

Central gray-white ill-defined opacities with diffuse stromal haze between deposits that progress deeper and eventually extend limbus-to-limbus

How is macular dystrophy managed?

Usually requires corneal transplantation, although PTK may help superficial opacities

How is Schnyder dystrophy inherited?

Autosomal dominant

What accumulates in Schnyder dystrophy?

Cholesterol and phospholipids within basal epithelial cells, Bowman's layer, and stroma

Which stains identify Schnyder dystrophy deposits?

Oil Red O and Sudan Black stains

What systemic conditions are associated with Schnyder dystrophy?

Hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and xanthelasma

Do all Schnyder dystrophy patients have visible crystals?

No, approximately 50% do not have crystals

What are the characteristic findings of Schnyder dystrophy?

Central ring- or disc-like opacities with or without yellow-white cholesterol crystals, stromal haze, progressive arcus senilis, and full-thickness stromal haze later in life

What laboratory testing should be ordered in Schnyder dystrophy?

Fasting lipid profile including cholesterol and triglycerides

How is Schnyder dystrophy managed?

Lipid evaluation, PTK for superficial opacities, and possibly corneal transplantation

What does PPMD stand for?

Posterior polymorphous dystrophy

How is posterior polymorphous dystrophy inherited?

Autosomal dominant

What tissues are abnormal in PPMD?

Descemet's membrane and endothelium