Corneal Dysttophys and endothelial dysfunction Flashcards
Define corneal dystrophy?
A group of inherited, bilateral, progressive diseases that lead to corneal opacification
What mutation is linked with many corneal dystrophies?
Mutations in the Transforming growth-factor B induced gene(BIGH1) on chromosome 5q31 (esp Bowmans and stromal layer)
What does BIGH1 code for? What do mutations here result in?
A protein expressed on the cell membrane of the corneal epithelium and stromal keratocytes which aids with wound healing
Mutations cause abnormal folding of the proteins and amyloid or non-fibrillar deposits. All are AD with Complete penetrance
What is iridocorneal endothelial syndrome?
A unilateral, sporadic disorder that occurs in Adults
What can be seen on specular microscopy in iridocorneal endothelial syndrome?
The corneal endothelium has degenerate endothelial cells which may be surrounded by normal cells
The endothelial cells form blebs and can acquire numerous microvilli on their posterior surface
These abnormal cells can act to form a membrane over the angle structure
What are late complications of iridocorneal endothelial syndrome?
Corneal decompensation and oedema
Glaucoma
What conditions are associated with Iridocorneal endothelial syndrome?
- Chandler syndrome - Glaucoma due to endothelial sliding with a normal Iris
- Progressive Iris stromal atrophy
- Presence of an iris naevus (Cogan-Reese syndrome)
What is Bullous keratopathy?
Occurs due to endothelial decompensation which leads to corneal oedema progressing from stromal to epithelial microcystic and then epithelial macrocystic (bullous) oedema
What is seen on examination in Bullous keratopathy?
Stromal oedema with DM folds
Followed by Epithelial oedema, subepithelial scarring and corneal neovascularisation
Name causes of Bullous Keratopathy.
- Fuch’s Endothelial dystrophy
- Intraocular surgery e.g. aphakic or pseudophakic BK more likely following complications or placement of an anterior chamber lens.
- Endothelial cell inflammation due to herpes simplex/zoster
- Corneal graft failure/rejection
- Chronic anterior uveitis
- Trauma
Name Epithelial dystrophies (2)
- Cogan’s microcystic dystrophy or Map dot dystrophy
- Meesman’s Dystrophy
Name Bowman’s layer dystrophies (2)
Reis- Bucklers’ Dystrophy
Thiel-Behnke Dystrophy
Name Stromal dystrophies (6)
- Lattice dystrophy
- Granular and Avellino dystrophy
- Avellino or granular lattice dystrophy
- Macular Dystrophy
- Schnyder crystalline dystrophy
- Gelatinous droplike dystrophy
What layer does Cogan’s microcystic dystrophy/map dot dystrophy affect?
Epithelium
Name Endothelial dystrophies
Congenital hereditary endothelial dystrophy
Fuchs’ endothelial dystrophy
Posterior Polymorphous dystrophy
What is the inheritance of Cogan’s microcystic dystrophy/map dot dystrophy? and Age of onset?
AD or Sporadic
2nd decade
What the histology of Cogan’s microcystic dystrophy/map dot dystrophy
Degeneration if cells with cyst formation leads to unstable epithelium
Histology shows:
- Thickened basement membrane
- Absent or abnormal hemidesmosomes
- Fibrillar material between basement membrane and Bowman’s layer
What layer does Meesman’s dystrophy affect?
Age of onset?
Epithelial
Early childhood
What the pathophysiology of Meesman’s dystrophy?
Separation of cells with deformation of neighbouring cells leading to formation of Loops of basement membrane and microcysts
What Layer does Reis- Buckler dystrophy affect?
Bowman’s layer
What is the inheritance of Reis- Buckler dystrophy? Age of onset?
AD - mutation of TGFB1
Early childhood/adult life
What is seen on examination in Reis- Buckler dystrophy?
Fine reticular opacity in the superficial cornea
What is seen on Histology in Reis- Buckler dystrophy?
Nodules of fibrous tissue between Bowman’s layer and epithelium
What is seen on Electron Microscopy in Reis- Buckler dystrophy?
Electron dense rods
What layer does Thiel-Behnke dystrophy affect?
Bowman’s layer
What is the inheritance of Thiel-Behnke dystrophy?
Age of onset?
AD - mutation links to chromosome 10
Usually affects older patients
What is seen on histology in Thiel-Behnke dystrophy?
Nodules of fibrous tissue between Bowman’s layer and epithelium
What is seen on Electron microscopy in Thiel-Behnke dystrophy?
Curly fibres within the superficial fibrous nodules
Granular and Avellino dystrophy affects which corneal layer?
Stromal
What is the inheritacne of Granular and Avellino dystrophy?
age of onset?
AD - Linked to TGFB1 gene
Early life
What is seen on examination in Granular and Avellino dystrophy?
White, well demarcated stromal deposits
What is seen on histology in Granular and Avellino dystrophy
Discrete opaque granules in the anterior stroma
What is substance is deposited in Granular and Avellino dystrophy?
Non birefringent HYALINE bodies with keratinoid
What is the stain for Hyaline?
Mason Trichome
What is seen on histology in Avellino dystrophy/granular lattice dystrophy?
Histologically and clinically the same as granular dystrophy - with the addition of amyloid deposits (as well as Hyaline)
- Discrete opaque granules in the anterior stroma
Which Layer does lattice dystrophy affect?
Stroma
What is the most common stromal corneal dystrophy?
Lattice
2nd - Granular
What is the inheritance pattern of Lattice Dystrophy?
age of onset?
Type 1 - AD, onset in 1st decade
Type 2 (rare) - AD, onset in 3rd decade
Co-exists with systemic amyloidosis
Type 3 - AR, onset in 5th decade
What is seen on microscopy in Lattice dystrophy?
Deposits of amyloid in the anterior stroma
What stains are used in Amyloid?
- Congo red: Stains orange red, apple green birefringence with polarised light
- Crystal violet
- Thioflavin T
What are some features of systemic amyloidosis?
- Dry lax skin
- Mask like facies
- Abnormal ears
- Cranial nerve palsies
What is the inheritance of Macular dystrophy? Age of onset?
AR
Onset in 1st decade
What is seen on examination in Macular dystrophy?
Focal grey white anterior stromal opacities in the axial region
What substance is deposited in Macular dystrophy?
Mucopolysacharide granules accumulate in the cytoplasm of keratocytes and in the adjacent interlamellar spaces when the cells rupture.
What is the Inheritance of Schnyder crystalline dystrophy?
AD (rare)
What condition is associated with Schnyder crystalline dystrophy?
Local disorder of corneal lipid metabolism
Strongly associated with systemic hypercholesterolaemia
What substance is deposited in Schnyder crystalline dystrophy?
Fine polychromatic cholesterol crystals in the anterior stroma with dense corneal arcus
What is the inheritance of Gelatinous droplike dystrophy?
age of onset
AR
1st decade with band keratopathy
Which layer does Schnyder crystalline dystrophy affect?
Stroma
What is Congenital Hereditary endothelial dystrophy?
- Primary dysfunction of corneal endothelial cells, leading to corneal opacification
- The endothelium may be attenuated and vacuolated
What is the inheritance of CHED?
2 types:
- CHED 1 - AD, 2nd year of life
- CHED 2 - AR, from birth to 1st few weeks of life
Is Fuch’s more common in Males or females?
Female
What is the inheritance of Fuchs?
AD or Sporadic
Describe the pathophysiology of fuchs?
Dystrophic endothelial cells
Lead to formation of guttata or excrescenes due to abnormal collagen deposition on a thickened DM
Reduction in number and function of cells leads to progressive corneal oedema
Persistent epithelial oedema can lead to Bullous keratopathy
What layer does posterior polymorphous dystrophy affect?
Endothelium
What is the inheritance of posterior polymorphous dystrophy?
AD
What is seen on histology in posterior polymorphous dystrophy?
Multilayered endothelial cells which have some features normally seen in epithelial cells e.g. microvillae
In severe diffuse disease - the posterior corneal surface is lined by stratified cells with prominent desmosomal attachments resembling corneal epithelial cells
What are the symptoms of posterior polymorphous dystropy?
Usually asymptomatic
But can lead to astigmatism or decompensation
What is deposited in macular dystrophy and what stains it?
Mucopolysacharide - Acian Blue
What is deposited in Granular dystrophy and what stains it?
Hyaline - Mason Trichome
What is deposited in Lattice dystrophy and what stains it?
Amyloid - Congo red/Crystal Violet/Thioflavin T
