Corneal Dystrophies, congenital anomaliesWafa Asfour FRSC

Dystrophies

Bilateral Symmetric inherited condition

Has little or no relationship to environmental or systemic factors

Tend to be slowly progressive

Begin early in life but may not become clinically apparent until later

Classification according to : severity, genetic, pattern, histo-pathologic features or anatomical location

Anterior Corneal Dystrophies

Corneal Epithelial dystrophy (EBMD)

Map-dot-fingerprint or Cogan

Most common anterior corneal dystrophy

Autosomal dominant with incomplete penetration 6-18% of population, commoner in women and > 5o years of age

Thickened basement membrane with extension into epithelium, abnormal epithelial cells with microcysts with absent or abnormal hemidesmosomes, fibrillar material between basement membrane and bowman layer

Clinical findings:

Age of onset of signs is probably 3rd decade while age of onset of symptoms is either 3rd or 4th decade of life

It is often asymptomatic, otherwise painful recurrent erosions, recur over several years with gradual reduction in frequency

Slit lamp signs most common and earliest change is a maplike pattern, best seen with sclerotic scatter, retroillumination or broad beam

Dots are fine, grey, round or comma shaped opacities seen deep to or bordering on maps

Fingerprints are rarest appear as concentric curved lines

Map-finger-dot epithelial dystrophy

Fine fibrillary line in a patient withanterior membrane dystrophy

Light Microscopy Maps: an abnormal basement membrane within the epithelial

layer separating it into anterior and posterior lamellae

Dots: Pseudocysts containing nuclear and cytoplasmic depris in the midepithelial layer

Fingerprints: are projections of basement membrane onto overling epithelium

Management:

5% Nacl ointment/ lubricants

Epithelial debridement

Patching /BCL

Meesmann Dystrophy

Rare bilateral Autosomal dystrophy

Appears early in life

Degenerated epithelial cells> producing frequent mitosis> thickened basement membrane , basal epithelial cells.

Have higher glucose, filamentary materials peculiar substance, tiny epithelial vesicles are seen most easily with retro-illumination extending out to limbus most numerous in the inter-palpebral area

Corneal dystrophy of Bowman’s layer

CDB type I (Reis-bucklers dystrophy) is Autosomal dominant has been linked to chromosome 5q 31

In same region as (lattice, Avellino, Granular)

Reis Buckler’s dystrophy: geographic has rod-shaped bodies in the region of Bowman’s, similar to superficial variant of granular dystrophy

CDB type II (Theil-Behnke dystrophy) is associated with

chromosome 10q 24

Honeycomb-shaped, or Theil-Behnke, dystrophy has {curly fibers}

REIS –BUCKLERS’ DYSTROPHY

Autosomal dominant

A bilaterally symmetrical dystrophy predominantly affecting Bowman’s layer of the central cornea

Age of onset of signs and symptoms 1st decade

Present as: Recurrent attacks of photophobia and irritation. Subsequently progressive visual loss due to:

1, anterior corneal opacification

2. irregular astigmatism

Recurrent erosions(3 or 4 episodes per year) gradually diminishing in frequency over 3 decades

REIS –BUCKLERS’ DYSTROPHY

Thiel- Behnke

Slit lamp signs

Fine reticular opacification at the level of Bowman’s layer

Irregular corneal surface

Largely grey white opacities in the subepithelial layer these may be linear, geographic, ringlike, honeycomb, fishnet or alveolar

It tends to spare periphery

The irregularity of corneal surface help to distinguish from Granular

fibrous tissue between epithelium and Bowman;s layer resulting in a saw tooth configuration of epithelium eventually replaces Bowman’s layer

Masson’s trichrome

Light microscopy

Lattice Dystrophy

One of the three classic stromal dystrophies most commonly characterised by branching refractile lines as suggested by it’s name. Lattice dystrophy type I is the classic type without systemic involvement, while type II is associated with systemic amyloidosis

Age of onset of symptoms and signs: usually in the first decade but sometimes the fourth decade or later

Usually presents as recurrent erosions or diminished vision, occasionally asymptomatic

Slit lamp signs Starts in the anterior and middle central stroma with

glassy translucent dots followed by translucent lattice lines

Spectrum of changes is broad and the classic branching lattice figures may not be present

The dots are not dissimilar to those found in granular dystrophy stroma in between the opacitiesis generally clear, can take on a diffuse ground glass appearance with progression of disease

The peripheral cornea is said to be spared, however our clinical experience shows that peripheral cornea commonly becomes involved in later cases

An irregularity and scarring occurs as a result of recurrent erosions

in early stages the translucent dots may be present without lattice lines, this can lead to difficulty in diagnosis

The characteristic glassy appearance of the dots distinguish them from the grey white opacities seen in granular dystrophy, the opacities in granular tend to have irregular margins and some have relatively clear centers

The clarity of the intervening stroma distinguishes it from macular dystrophy

Recurrent erosions in lattice dystrophy lead to central subepithelial scarring which may be confused with Reis Bucklers’ , however by this stage the typical branching lattice lines are present

Light microscopy 1. Irregular epithelium

2. Thickened basement membrane

3. Large fusiform eosinophilic deposits in stroma

A. stain red with congo red

B. manifest green birefringence with a polarising microscope

C. display dichroism

D. fluoresce with thioflavin T and Ultraviolet light

Associations:

Lattice dystrophy may be associated with systemic amyloidosis. In this case it is called lattice dystrophy type II onset of stromal dystrophy tends to be later, the erosions less frequent, vision less affected than in lattice dystrophy type I without systemic involvement

Systemic involvement is characterised by cranial neuropathy, peripheral neuropathy, and skin masses

Lattice type II: fewer lattice lines and a greater involvement of peripheral cornea

Autosomal Dominant

Granular Dystrophy One of the three classic stromal dystrophies it is

characterized by discrete grey white deposits in the central anterior stroma

The intervening stroma is essentially clear and vision is not affected until late stages

Age of onset of signs is first decade while symptoms start in third decade or later

Most patients are asymptomatic mild photophobia may be present due to scattering of light by the opacities. recurrent erosions are very unusual, vision is usually not affected until the fifth decade

Slit lamp signs Discrete grey white dots or radial lines in the anterior

central stroma

The opacities enlarge, multiply and coalesce with time they gradually extend deeper into the stroma and further peripherally with time , however the peripheral 2-3 mm of the cornea are always spared making the distinction from macular dystrophy easy, the stroma in between the opacities remains clear

Light microscopy: eosinophilic rod or trapezoidal deposits in the anterior stroma, these stain red with Masson’s trichrome

Autosomal dominant

Advanced Granular Dystrophy

Advanced Granular Dystrophy

Avellino Dystrophy (Granular Lattice)

A variant of granular dystrophy, was originally described in a small number of famillies who traced their roots to Avellino, Itally

Avellino corneal dystrophy

It is also present in other countries; in Japan, it may be more common than lattice

The affected patients have a granular dystrophy both histologically and clinically, with lattice lesions in addition to the granular lesions

Older patients have anterior stromal haze between deposits which reduces visual acuity

Pathologically both the hyaline deposits typical of granular dystrophy and the amyloid deposits typical of lattice dystrophy

Clinical profile of Avellino corneal dystrophy in British families

Clinical and genetic profile of Avellino corneal dystrophy in 2 families from North India

Clinical and genetic profile of Avellino corneal dystrophy in 2 families from North India

Clinical and genetic profile of Avellino corneal dystrophy in 2 families from North India

Clinical and genetic profile of Avellino corneal dystrophy in 2 families from North India

Clinical and genetic profile of Avellino corneal dystrophy in 2 families from North India

Severe form of corneal stromal dystrophy in 5 Japanese patients

Clinical profile of Avellino corneal dystrophy in British families

Association of Keratoconus and Avellino Corneal Dystrophy

Macular Dystrophy

Is the rarest of the three classical stromal dystrophies

Uniquely it is inherited in an autosomal recessive manner

Characterized by multiple irregular grey white opacities in the superficial central corneal stroma with a diffuse stromal haze in between the lesions

Age of onset of signs and symptoms is the first decade

Macular Dystrophy

presentation

Photophobia is a prominent feature, out of proportion to the signs

Deterioration in vision occurs early, usually by 20 to 30 years of age

Penetrating keratoplasty is required

Recurrent erosions may occur but are much less frequent than in lattice dystrophy

Slit lamp signs

Earlier changes are a central, faint ground glass haze in the superficial stroma,

Later multiple small grey white opacities with irregular borders develop within this superficial haze.

Opacities are most dense centrally peripheral cornea is not spared the opacities may enlarge and take on a nodular appearance

Descemet’s membrane may take on a slate grey appearance and multiple corneal guttae may be seen until the stromal opacification precludes their view

Advanced Macular Dystrophy

Macular dystrophy may be difficult to distinguish from grnular in the early stages however in macular dystrophy:

A. there is an early intervening stromal haze

B. it involves deep and peripheral stroma

3. it is characterised by thinning of central stroma

4. there is an autosomal recessive history

Light microscopy

Distended vacuolated keratocytes with pyknotic nuclei

non-specific epithelial changes with degeneration of the basal epithelial cells and a slightly irregular Bowman’s layer

Stained for immunoglycans macular dystrophy is characterised by accumulations within and around stromal keratocytes in the subepithelial area Bowman;s layer, Descemet’s membrane and even endothelium

It stains blue with Alcian blue but also shows positive staining with PAS, colloidal iron and metachromatic dyes

Stromal Corneal Dystrophies

Macular Dystrophy- Mucopolysaccharide Alcian Blue

Granular Dystrophy –Hyaline materials- Masson Trichrome

Lattice Dystrophy – Amyloid- Congo red

Management

Central cloudy dystrophy of Francois

Fine described by Francois in 1956 this is a bilateral, symmetrical and non-progressive condition which usually does not affect vision or require treatment

Age of onset of signs is probably in the first decade, and usually asymptomatic, diagnosed on routine examination

Slit Lamp signs: multiple grey opacities in the deep stroma of the central two thirds of the cornea separated by narrow lines of clear stroma

The appearance is that of a mildly opacified cornea with cracks within it

This mosaic pattern is identical to the condition termed posterior Crocodile Shagreen by Vogt

This term is only given when there is a strong family history of the condition. It is autosomal dominant

Cloudy dystrophy of Francõis

Crystalline dystrophy of Schynyder

Rare, slowly progressive, Autosomal dominant Could present as early as 1st year of life, might not be diagnosed until later in 2nd or 3rd decadeIt is a localized disorder of corneal lipid metabolism ( unesterified and esterified cholestrol and phospholipidsClinical findings:a. Central subepithelial crystals (in 50% of patients)b. Central corneal opacificationc. Dense corneal arcus lipoidesd. Midperipheral corneal opacificationFasting lipid profile is necessary; for possible hyperlipoproteinemia (type II-a, III, or IV) or hyperlipidemia

Gelatinous droplike dystrophy

Primary familial Amyloidosis

Uncommon, Autosomal recessive

Subepithelial deposits

1st decade, may resemble band keratopathy

Endothelial Dystrophies

Fuch’s Dystrophy

Posterior polymorphous dystrophy

Congenital Hereditary Endothelial Dystrophy

Fuch’s Dystrophy The most commonly recognised endothelial dystrophy

chararcterised by corneal guttata, stromal and epithelial oedema

Corneal guttata may be recognised in the 4th or 5th decade in asymptomatic patients

Age of onset of symptoms is usually after the 6th decade of life

Women are affected more frequently and more severely than men

It should be noted that up to 70% of patients over the age of 40 years have guttae, however most of these never get classic Fuch’s dystrophy

Patients present with decrease in vision which characteristically is reported being worse first thing in morning but gradually improving through the course of the day

Later stages patients may complain of pain secondary to ruptured epithelial bullae

The dystrophy shows gradual progression over several decades leading eventually to the need for penetrating keratoplasty

Slit lamp signs 1. Corneal guttae are the earliest sign, patients may be asymptomatic,

guttae may be pigmented but should not be confused with simple pigment dusting of the endothelium

With direct illumination the guttae appear as refractile mounds on the posterior corneal surface most obvious centrally then spread towards the periphery to involve the wholeposterior surface of the cornea

Descemet’s membrane has a beaten metal appearance and is thickened, a diffuse mottled appearance may be appreciated against a red reflex guttae may be in association with other conditions:

Interstitial keratitis, macular stromal dystrophy, following uvietis, following trauma

2. stromal oedema and epithelial oedema: this Following failure of the endothelial pump, first occuring in the morning tending to clear through the course of the day

Slit lamp signs Signs of stromal oedema:

i. Folds in Descemet’s membrane

Ii. Stromal haze

Iii. Stromal thickening

Iv. Clear lines of spikes within the stromal haze

Signs of epithelial oedema:

i. clouding of anterior crnea

Ii. Microcyts

Iii. Fingerprint lines in the epithelium

Iv. Intra or subepithelial bullae

Subepithelial scarring this follows chronic corneal oedema, corneal sensation is reduced, can be complicated by erosions, vascularization and calcific degeneration

Light microscopy

Thickened descemet’s membrane

Excrescences of descemet’s membrane

Endothelial cells are larger and more polymorphic than normal

In longstanding cases subepithelial fibrosis is apparent

In families of affected patients, approximately 40% of blood related relatives over the age of 40 years have confluent corneal guttae

But it does not follow a strict Mendelian pattern

Endothelial cells are larger and more polymorphic than normal

beaten metal appearance

Posterior polymorphous dystrophy

A disorder of corneal endothelium characterised by variable findings including vesicles, bands and thickening of Descemet’s membrane which can be associated with both stromal and epithelial oedema

Occasionally the peripherl anterior synechae and broad iridocorneal adhesions with ectropion uvea can occur making it necessary to distinguish this condition from I.C.E syndromes

Age of onset of signs congenital, signs my not be recognised for many years, onset of symptoms are highly variable but usually in the first 2 decades

Patient may present with a decrease in vision due to corneal oedema and irregular pupil due to ectropion uvea or completely asymptomatic

Distinguished from Chandler’s syndrome, by the fact that it is bilateral and that it is dominantly inherited

Slit lamp signs

Corneal vesicles at level of corneal endothelium which can be isolated or coalescent and usually unassociated with corneal oedema

Thickening of Descemet’s membrane

Bands or thick lines on the posterior corneal surface resembling breaks in Descemet’s

Diffuse stromal or epithelial oedema

Peripheral anterior synechiae or broad based iridocorneal adhesion

Ectropion uvea

Raised intraocular pressure

Posterior polymorphous endothelial  dystrophy

Congenital Hereditary Endothelial Dystrophy

There are two forms of this disease , sever form autosomal recessive type, presents with corneal clouding at birth and accompanied with Nystagmus In the autosomal dominant type the corneal clouding appears later, slowly progressive with less often nystagmus

The autosomal recessive is present at birth, while the signs appear in first decade in autosomal dominant

Present with corneal clouding, nystagmus, no tearing or photophobia

In autosomal dominant type, pain, photophobia, & tearing accompany VA deterioration, no nystagmus

slit lamp signs

Diffuse corneal edema with marked stromal thickening giving the cornea a ground glass appearance

Epithelial oedema this is usually diffuse and non bullous

More dense white stromal opacities may occur within the edematous stroma

No systemic associations

Ectatic Disorders

Keratoconus

Posterior Keratoconus

Keratoglobus

Pellucid marginal degeneration

Kertoconus A non inflammatory stromal thinning disorder leading to a

localized conical protrusion of the cornea the thinning is most marked at the apex of the cone

Age of onset of signs and symptoms second decade

Patients present with progressive reduction in visual acuity, distortion, photophobia or symptoms of glare, examination reveals high irregular, myopic astigmatism and a scissoring reflex on retinoscopy. If keratometry is performed the central mires cannot be superimposed. Most cases are bilateral but often asymmetrical. The condition progresses to the age of 30 and then tends to stabilize.

Slit lamp signs

A conical protrusion of the thinned cornea which is usually eccentrically located with it’s apex inferior to the horizontal midline

A Fleischer ring

Vogt’s striae (fine vertical folds stroma and Descemet’s membrane parallel to the steep axis of the cone) the striae disappear with digital pressure on the globe

Anterior stromal scars following breaks in Bowman’s layer

Thickened corneal nerves

Acute stromal edema (hydrops) follows tears in Descemet’s membrane these resolve over several months leaving a scar. The cone may flatten after this and if the scar happens to be off axis the visual acuity may actually improve

Munson’s sign (deformation of the lower lid on down gaze)

Rizzuti’s sign a sharply focused beam of light near the nasal limbus produced by lateral illumination of the cornea. The beam is more central in earlier cases but moves peripherally as the cone progresses

Early cones are most easily detected with corneal topography and this can assist with the diagnosis before slit lamp signs appear

Light Microscopy:

Irregularity of and breaks in Bowman;s layer

Fibrous tissue forms in areas of breaks

Folding of anterior stromal lamellae

PAS positive granular substance surrounds these lamellae

The epithelium is thin with deposition of ferritin (both intra and extra cellular) in basal epithelium

Thinning of stroma (due to a decrease in the number of lamellae)

In acute hydrops:

Stromal oedema

Descemet’s membrane separates from the stromal and retracts into scrolls

Association

1. Atopic disease (atopic dermatitis, hay fever, asthma and vernal keratoconjunctivitis)

2. Down’s syndrome

3. leber’s congenital amaurosis

4. Mitral valve prolapse

There are also scattered reports of associations with Marfan’s syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta

Inheritance: not clearly established. A family history is present in approximately 8%

keratoglobus Very rare, bilateral, non-inflammatory

Typically present at birth

Usually not heriditary

Strongly associated with blue sclera and Ehlers -Danlos syndrome type VI

May represent a defect in collagen synthesis

Fragmented Bowman’s layer, thinned stroma and thin Descemet’s membrane

Eye-Protection (Rupture globe)

Carries poor prognosis for PK

Posterior keratoconus

A rare abnormality characterized by a concavity of the posterior corneal surface in association with a normal anterior corneal curvature. The concavity may be focal, usually inferior, or diffuse. Most cases are in females and are unilateral

It is congenital

Scarring may be noted in the cornea anterior to the area of concavity. The condition may be observed in assessing a child with suboptimal vision due to associated abnormalities: retinal coloboma, optic nerve hyperplasia or congenital cataract

Slit lamp signs

Concavity of the posterior corneal surface with a normal anterior corneal curvature usually focal and inferior

Scarring in the stroma anterior to this concavity

Endothelial guttae

Thickening of Descemet’s membrane around the area of concavity

Associated ocular abnormalities: posterior synechiae

Light Microscopy

Characteristic conical posterior surface with loss of stromal substance

Disruption of normal lamellar arrangement of corneal stroma with variable degrees of fibrosis

Absence of Bowma’s layer centrally

Excrescences of Descemet’s membrane

Inheritance: sporadic

Pellucid Marginal Degeneration

A bilateral inferior peripheral corneal thinning with protrusion of the cornea above it.

It needs to be distinguished from keratoconus and Terrien’s marginal degeneration

Age of onset of signs and symptoms is 3rd decade

Patient’s present with a gradual deterioration in vision due to high irregular astigmatism

There is thinning of the peripheral cornea approximately 1-2 mm from the limbus and concentric to it usually extending from 4 to 8 o’clock and being approximately 1-2 mm wide

Pellucid marginal degeneration

Above this thinned area is a protrusion of the cornea which protrudes inferiorly giving a beer belly appearance in cross section

The central cornea is of normal thickness.

Vertical stress lines and hydrops are much less common than in keratoconus.

distinguished from keratoconus , protrusion occurs above an area of thinning , thinning is at the apex of cone in keratoconus

Terrien’s marginal degeneration, avascular and free of lipid deposition.

Mooren’s ulcer: occurs in a white eye and the thinned area is epithelialised

Inheritance is not known