CORNEAL DYSTROPHIES

AND ECTASIAS
RUTH ANTOLIN
SECOND YEAR
DOH EYE CENTER

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CORNEAL DYSTROPHIES

Bilateral
Symmetric
Inherited
Little environmental/ systemic factors
Slowly progressive becomes more apparent with age

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CLASSIFICATION OF CORNEAL DYSTROPHIES

International Committee for the classification of

corneal dystrophies (IC3D) (AAO p.254)

Anatomical
4 categories

1 well defined; gene mapped and identified; mutations

known
2 well defined; mapped to specific chromosome loci;
gene NOT known
3 well defined; NOT yet mapped
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4 suspected new, previously documented; evidence
NOT yet convincing

IC3D CLASSIFICATION OF MAJOR CORNEAL

DYSTROPHIES

Epithelial and Subepithelial

Bowman Layer
Stromal

TGFB1
Non TGFB1

Descemet Membrane and Endothelial

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EPITHELIAL AND SUBEPITHELIAL

DYSTROPHIES

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EPITHELIAL BASEMENT MEMBRANE DYSTROPHY

(EBMD)

Map dot fingerprint dystrophy, Cogan microcystic

epithelial dystrophy, anterior basement membrane
dystrophy
Sporadic, degenerative
Abnormality of epithelial turnover, maturation
and production of BM

Thickened BM with extension into the epithelium

Abnormal epithelial cells with microcyst
Fibrillar material between and basement membrane and
Bowman layer
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EPITHELIAL BASEMENT MEMBRANE DYSTROPHY

(EBMD)

Seen in 6%- 18% of

population, more common
in women, age > 50
Examination:

Fingerprint linesMap linesDots/ microcysts

Bleb/ cobblestone- like
pattern
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EPITHELIAL BASEMENT MEMBRANE DYSTROPHY

(EBMD)

Signs and Symptoms

Recurrent epithelial erosions (50%)
Transient blurring of vision
irregular astigmatism
BOTH EYES must be examined
UNILATERAL EPITHELIAL BASEMENT MEMBRANE
CHANGES:
Trauma > dystrophy
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MEESMANN EPITHELIAL CORNEAL DYSTROPHY

Juvenile hereditary epithelial dystrophy; Stocker- Holt

Autosomal dominant
Locus 12ql3; gene: keratin K3 (KRT3); Stocker-Holt variant:
17q12; gene: keratin K12 (KRT12)
Epithelial microcyst accumulation of granular and
filamentary material
Frequent mitoses and thickened basement membrane
projecting to the basal epithelium
Confocal microscopy: hyporeflective areas in the basal
epithelium 40-150 um
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MEESMANN EPITHELIAL CORNEAL DYSTROPHY

Signs and symptoms:

Small epithelial vesicles
(retroillumination) in the
INTERPALPEBRAL AREA
Slightly thinned cornea
Reduced corneal sensation
Mild irritation and slight
decrease in vision
Management: soft contact
lens
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LISCH EPITHELIAL CORNEAL DYSTROPHY

Band shaped and whorled microcystic

dystrophy of the corneal epithelium
X chromosomal dominant
Locus Xp22.3; gene unknown
DIFFUSE cytoplasmic vacuolization (light and
transmission electron microscopy)
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LISCH EPITHELIAL CORNEAL DYSTROPHY

Immunochem: scattered staining Ki67 without

increased mitotic activity
Confocal microscopy: Solitary dark round and
oval lesions (50-100um)

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LISCH EPITHELIAL CORNEAL DYSTROPHY

Signs and symptoms:

Discrete sectorial, gray,
band- shaped and
feathery lesions in
whorled patterns
CROWDED, clear microcyst
Painless, decreased vision

Mx: contact lens,

debridement
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GELATINOUS DROPLIKE CORNEAL DYSTROPHY

Subepithelial amyloidosis, primary familial amyloidosis

Autosomal recessive
Locue 1p32; gene : tumor- associated calcium signal
transducer 2 (TACSTD2)
Subepithelial and stromal AMYLOID DEPOSITS
High epithelial permeability

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GELATINOUS DROPLIKE CORNEAL DYSTROPHY

Signs and symptoms:

1st to 2nd decade
Band keratopathy
Mulberry configuration: groups of multiple small nodules
Kumquat lesions: stromal opacification/ larger nodular
lesions

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GELATINOUS DROPLIKE CORNEAL DYSTROPHY

Management:

Superficial keratectomy
Lamellar keratoplasty
Penetrating keratoplasty
Soft contact lenses

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BOWMAN LAYER CORNEAL

DYSTROPHIES

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REIS- BUCKLERS CORNEAL DYSTROPHY

Corneal dystrophy of Bowman layer type 1 (CDB1),

geographic corneal dystrophy,
Autosomal dominant
Locus 5q31; gene TGFB1
Disrupted/ absent Bowman layer : sheetlike tissue with
granular Masson trichome red deposit

TGFB1 keratoepithelin positive

Elevation of the corneal epithelium corneal erosion
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REIS- BUCKLERS CORNEAL DYSTROPHY

Signs and Symptoms

Geographic opacities
with varying densities
in the Bowman layer
and stroma (central)
1st/ 2nd decade
Eye pain, photophobia,
BOV
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REIS- BUCKLERS CORNEAL DYSTROPHY

Management:
Superficial keratectomy
Lamellar keratoplasty
Phototherapeutic keratectomy
Penetrating keratoplasty

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THIEL-BEHNKE CORNEAL DYSTROPHY

Corneal dystrophy of Bowman Layer Type 2

Autosomal dominant
Loci 5q31, 10q24; gene TGFB1 (5q31), unknown
(10q24)
Thickening of the epithelial layer

Ridges and furrows in the stroma

Focal absence of the epithelial basement membrane

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THIEL-BEHNKE CORNEAL DYSTROPHY

Fibrocellular material in a
wavy, saw toothed
pattern in the Bowman Layer
Electron microscopy: curly
fibers

TGFB1 positive

Confocal microscopy:
Epithelium: highly reflective with round edges and
dark shadows
Bowman: less reflective

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THIEL-BEHNKE CORNEAL DYSTROPHY

Signs and symptoms:

Symmetric, subeptihelial,
reticular (honeycomb)
opacities sparing the
peripheral cornea
Eye discomfort/ pain
Deterioration of vision

Management: as RBCD

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STROMAL CORNEAL
DYSTROPHIES
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TGFB1 DYSTROPHIES

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LATTICE CORNEAL DYSTROPHY

LCD Type 1, Classic LCD, Biber- Haab- Dimmer

Autosomal Dominant
Locus 5q31; gene TGFB1
Amyloid deposits in the anterior stroma
Eosinophilic layer between the epithelial basement
membrane and Bowman layer develops
Congo red: (+) rose to orange red stains
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LATTICE CORNEAL DYSTROPHY

Birefringence and dichromism

Electron microscope: electrodense fibrils with random
alignment
Confocal microscopy: linear images

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LATTICE CORNEAL DYSTROPHY

Signs and symptoms

Glasslike branching lines in the stroma
Ground glass appearance
Clear periphery
Refractile lines best seen on retroillumination
Lines begin centrally and superficially
centrifugally and deeper
Decreased visual acuity
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LATTICE CORNEAL DYSTROPHY

Contact lenses
Superficial keratectomy/
PTK
Severe cases: Deep
anterior lamellar
keratoplasty (DALK) or
PK
Recurrence: 9 years
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LATTICE CORNEAL DYSTROPHY2

Gelsolin type (LCD2); Familial amyloidosis,

Finnish type (FAF); Meretoja syndrome
Autosomal dominant
Locus 9q34; gelsolin (GSN)
Amyloid under the Bowman layer and within
sclera
Diffuse deposition of amyloid in arterial walls,
peripheral nerves

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LATTICE CORNEAL DYSTROPHY2

Signs and symptoms

3rd to 4th decade
Ocular adnexae
deposition
Increased risk for open
angle glaucoma
LESS numerous MORE
peripheral lattice lines
cetntripetally spread
Reduced corneal
sensation

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GRANULAR CORNEAL DYSTROPHY (1)

Groenouw corneal dystrophy type 1

Autosomal dominant
5q3p1; TGFB1
Hyaline (+) Masson trichrome stain
Electron Microscopy: electron dense rod shaped
bodies
Histo: noncollagenous protein
Confocal microscopy: hyper reflective opacities
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GRANULAR CORNEAL DYSTROPHY (1)

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GRANULAR CORNEAL DYSTROPHY (1)

Signs and symptoms:

Crumb like opacities in
the superficial cornea
Do not extend to the
limbus
Extend anteriorly
through focal breaks in
the Bowman layer
Slowly progressive
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GRANULAR CORNEAL DYSTROPHY (1)

No treatment if mild
DALK or PK if VA affected
Recurrence: fine subepithelial opacities

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GRANULAR CORNEAL DYSTROPHY (2)

Combined granular- lattice corneal dystrophy, Avellino

corneal dystrophy
Autosomal dominant
5q31; TFB1
Hyaline and amyloid deposits from epithelium to
deep stroma
Masson/ Congo red stain positive
Rod shaped bodies
Confocal microscopy: linear images and hyper
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reflective opacities
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GRANULAR CORNEAL DYSTROPHY (2)

Signs and symptoms

Granular + lattice
Stellate shaped
between superficial
stroma and midstroma
Stromal haze between
deposits
Pain
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GRANULAR CORNEAL DYSTROPHY (2)

Management:
Depends on the
depth
PTK contraindicated

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NON TGFB1 DYSTROPHIES

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MACULAR CORNEAL DYSTROPHY (MCD)

Groenouw corneal dystrophy type II, Fehr spotted

dystrophy
Autosomal recessive
16q22; carbohydrate sulfotransferase 6 (CHST6)
Glycosaminoglycans deposits: Alcian blue and
colloidal iron
Accummulation in the ENDOPLASMIC RETICULUM
Electron microscopy: keratocytes and endothelial cells
Confocal microscopy: Blurred light reflective 40 of
material in the anterior stroma
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MACULAR CORNEAL DYSTROPHY (MCD)

Signs and symptoms:

Stromal, peripheral and
corneal endothelium
Progressive clouding (ages
3- 9)
Focal, gray- white,
superficial stromal opacities
extending to the corneal
periphery
Indefinite edges
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MACULAR CORNEAL DYSTROPHY (MCD)

(+) corneal guttae:

involvement of DM
and endothelium
Epithelial erosions:
decrease in vision
Central corneal
thinning
Hypoesthesia

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MACULAR CORNEAL DYSTROPHY (MCD)

Type I

Prevalent form
Error in the SULFATION
of keratin sulfate
synthesis
IA:
AgKS reactivity in
keratocytes

Type II

Normal ratio keratin:

dermatan sulfate
Total synthesis >
30% normal
Dermatan sulfate >
40% shorter
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MACULAR CORNEAL DYSTROPHY (MCD)

Diagnosis:
Clinical
ELISA
Management:
Tinted contact lenses
PTK: anterior macular dystrophy
PK- definitive treatment
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SCHNYDER CORNEAL DYSTROPHY

Schnyder crystalline corneal dystrophy, crystalline

stromal dystrophy, central stromal dystrophy
Autosomal dominant
1p36 gene: (UB1AD1)
Disorder of corneal lipid metabolism
Accumulation of lipid : opacities
Confocal microscopy: disruption of epithelial/
subepithelial nerve plexus
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SCHNYDER CORNEAL DYSTROPHY

Signs and symptoms

CENTRAL CORNEAL
OPACIFICATION +
CENTRAL
SUBEPITHELIAL
CRYSTALS
DENSE CORNEAL ARCUS
LIPOIDES
MIDPERIPHERAL corneal
opacification

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SCHNYDER CORNEAL DYSTROPHY

Management
PKP
PTK- subepithelial
crystals
Diet/ medication: but
does not affect
progression
Check
Hyperlipoproteinemia/
hyperlipidemia

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CONGENITAL STROMAL DYSTROPHY

Congenital hereditary stromal dystrophy

Autosomal dominant
12q21.33; decorin
Collagen fibril diameter half of the normal
Absence of anterior banded zone of DM
Increased reflectivity of stromal evaluation
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CONGENITAL STROMAL DYSTROPHY

Signs and symptoms:

Diffuse, bilateral clouding
Flakelike whitish stromal
opacities
Thick
Vision loss

Management: PK
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FLECK CORNEAL DYSTROPHY

Francois- Neetens speckled corneal dystrophy

Autosomal dominant
2q35; gene: PIP5K3
Vacuolated keratocytes:

Excess GAGs
Excess lipids

Pathologic material in stroma and inclusions in

basal nerves
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FLECK CORNEAL DYSTROPHY

Signs and Symptoms:

Discrete, flat, graywhite, dandruff like

(sometimes ring shaped)
stromal opacities
Extends to periphery
Minimal symptoms
Non progressive,
asymptomatic, unilateral
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FLECK CORNEAL DYSTROPHY

Associated with:
Decreased corneal sensation
Limbal dermoid
Keratoconus
Central cloudy dystrophy
Punctate cortical lens changes
Pseudoxanthoma elasticum
Atopy

No management
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POSTERIOR AMORPHOUS STROMAL DYSTROPHY

Autosomal dominant
No identified gene locus
Focal attenuation of
endothelial cells and
irregular stromal
architecture anterior to the
Descemets membrane
Disorganized posterior
stromal lamellae: microfolds
Appears during the first
decade

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POSTERIOR AMORPHOUS STROMAL DYSTROPHY

Diffuse, gray white sheetlike

opacity
Slowly progressive, non
progressive
Cornea: flat ( <41D) and
thin ( < 380um)
Hyperopia
Opacities seen on the DM and
endothelium
Vision is mildly affected
Management: None; PK

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PRE DESCEMET CORNEAL DYSTROPHY

No definite pattern of inheritance

No identified gene locus
Large keratocytes in the posterior stroma
Vacuoles
Intracytoplasmic inclusions- lipid
EM:
Vacuoles: electron dense = lysosomes
Inclusions: lipofuscin like lipoproteins
Degenerative

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PRE DESCEMET CORNEAL DYSTROPHY

Focal, fine, gray opacities seen in the deep stroma

anterior to the DM
Onset: after age 30
Vision is normal
Associations:

Pseudoxanthoma elasticum
Ichthyosis
Keratoconus
PPCD and EBMD
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ENDOTHELIAL DYSTROPHIES

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FUCHS ENDOTHELIAL CORNEAL DYSTROPHY

Endoepithelial corneal dystrophy, endothelial corneal

dystrophy
Most common cases: no known inheritance; Autosomal
dominant inheritance
Locus 13pTel- 13q12.13, 15q; chromosome 18
Transcription factor 4 (TCF4)
Polymegathism and pleomorphism
Excess collagen : by product of stressed endothelial
cells
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Reduction in the number of Na-K pump sites
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FUCHS ENDOTHELIAL CORNEAL DYSTROPHY

Guttae centrally
peripherally
DM folds
Endothelial pigmentation
CCT: 1mm
Microcystic edema
epithelial bullae
rupture sub epithelial
fibrosis
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FUCHS ENDOTHELIAL CORNEAL DYSTROPHY

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FUCHS ENDOTHELIAL CORNEAL DYSTROPHY

Signs and symptoms:

Blurring of vision
Pain upon awakening
Diagnostics:
Specular microscopy:
< 1000/mm2
Corneal pachymetry >
640um
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FUCHS ENDOTHELIAL CORNEAL DYSTROPHY

Management:
NaCl drops and ointment
IOP lowering agents
BCL
Severe cases: anterior stromal puncture,
Amniotic membrane, conjunctival flap
PKP/ EK
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POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY

PPMD, Schlichting dystrophy

Autosomal dominant
PPCD1, PPCD2 (COL8A2), PPCD3 (ZEB1)
Abnormal, multilayered endothelial cells appearing/
behaving like fibroblast or epithelial cells
Diffuse DM thickening
Multilaminated and polymorphous
Similar changes in ICE syndrome
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POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY

Diffuse abnormality of the

DM
Membrane thickening
Multilaminated
appearance
Polymorphism/
polymegathism
Specular microscopy:
vesicles and bands
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POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY

Confocal microscopy: DM
alterations;
polymegathism of
endothelial cells

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POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY

Isolated grouped vesicles

Geographic, discrete, gray
lesions
Broad bands with
scalloped edges
Associated findings:

Stromal edema,
corectopia, iridocorneal
adhesions, IOP elevation
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POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY

Management:

NaCl topicals
Stromal micropuncture
Anti glaucoma medications
PKP

Depends on the PAS and glaucoma

EK for earlier cases without stromal opacification

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CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY

Autosomal dominant
Locus 20p11.2-q11.2
Diffuse thickening and lamination of the DM
Atrophic, sparse endothelial cells
Keratinized endothelium
EM:

thickened stroma
Disorganized and disrupted lamellae
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CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY 1

First or second year of life
Diffuse corneal clouding (110 years) and thickening
Irregular peau dorange
endothelium
Endothelial
decompensation
Management:
PK/ EK in advanced cases

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CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY 2

Maumenee corneal dystrophy

Autosomal recessive
Locus 20p13; SLC4A11
Same pathology as CHED1 but more severe
Focal gray spots and clouding: diffuse haze to ground
glass appearance
Subepithelial band K (rare); IOP elevation
Management: Corneal transplant
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ECTATIC DISORDERS

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KERATOCONUS

Prevalence: 1/2000
Cprogressive thinning and bulging of the
central/ paracentral cornea
Family history: 6-8%
Combination of genetic and environment risk
factors:
Eye rubbing Inflammatio Atopy
n
Hard
Oxidative
contact lens
stress
wear

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KERATOCONUS

Histology:
Fragmentation of the Bowmans
Epithelium and stromal thinning
DM folds/ Breaks
Diffuse scarring

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KERATOCONUS

Bilateral
Progression during adolescent and into mid 20s
Videokeratoscopy: enantiomorphism

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KERATOCONUS

Biomicroscopic signs:

Fleischer ring
Vogt striae
Apical corneal scarring

Histologic Findings:

Fibrillation of Bowman
layer
Fibrous growth/
dysplasia break
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KERATOCONUS

Scissoring of the red reflex on ophthalmoscopy

Rizzutti sign
Munson sign

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KERATOCONUS

Acute hydrops
Allergy/ Eye rubbing
heals spontaneously in 6-12
weeks
Scarring
Associations:
Down/ Marfan syndromes
Floppy eyelid
Leber congenital optic
neuropathy
Mitral valve prolapse

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KERATOCONUS

Evaluation

Computerized
videokeratography:
detection, contact lens
ftting
Placido disk based
topography
Pachymetry
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KERATOCONUS

Management:

Glasses/ rigid contact lenses

Nodulectomy: removal of central
subepithelial scar
Intrastromal rings
Collagen cross linking
Corneal transplant: PK/ DALK
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KERATOCONUS

Acute hydrops:

Topical hypertonic agents + patching/ contact lensacute hydrops

Cycloplegic agent
Aqueous suppressants
Intracameral injection of gas

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PELLUCID MARGINAL DEGENERATION

Rare, non hereditary,

bilateral
Non inflammatory;
Idiopathic
Protrusion of the cornea
above the band of thinning
High irregular astigmatism
20- 40 years old
M= F
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PELLUCID MARGINAL DEGENERATION

Management:
Contact lenses (early):
Hybrid/ Scleral lens
PK- vision restoration
Large grafts; close to the
limbus
Wedge resection/
Lamellar tectonic grafts
Collagen cross linking
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KERATOGLOBUS

Rare, bilateral, non

inflammatory
Present at birth
Not hereditary
Globular deformation of
the conea

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KERATOGLOBUS

Associations:

Blue sclerae
Ehler Danlos syndrome Type IV

May represent a defect in collagen synthesis

Histologically:

absent/ fragmented Bowmans layer

Thinned stroma and Descemets
Normal lamellar organization
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KERATOGLOBUS

Globular shaped corneas:

50-60D
Generalized corneal
thinning- midperiphery
Very deep anterior
chamber
Slightly increased corneal
diameter
DM folds and thickening
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KERATOGLOBUS

Management:

Contact lenses- scleral lens

Corneal transplant- poor prognosis

Lamellar tectonic graft followed by PK

Protective eyewear
Correction spectacles:

Myopia
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THANK YOU!

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