corneal dystrophies
TRANSCRIPT
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