Corneal Disorders Epi to Endo

Corneal Disorders
Epi to Endo
Christine W Sindt OD FAAO
University of Iowa
Director, Contact Lens Service
Associate Professor of Clinical Ophthalmology
1
Corneal Epithelium: Anatomy
Thickness of epi?
Time to turnover?
Time for production of
basement membrane?
Components of b.m.?
• 40-50u
• 7-10 days
• 6 weeks
• Collagen IV
• Laminin
• Fibronectin (during
active epithelial
injury)
2
Corneal Epithelium: Wound
Healing
Healing from injury:
„immediate cell migration and spreading in smaller
injuries, delay of 4-5 hours in larger injuries
„migrates at rate of up to 60-80um/hr
„mitosis and proliferation begins at 24hrs for smaller
injuries, up to 96hrs for larger injuries
„X, Y, Z hypothesis: proliferate, migrate, desquamate
„all this is affected by ocular surface disease
3
Corneal Epithelium: Wound
Healing
„diabetes: thickened b.m.
„neurotrophic: lack of substance P?
• DDx?
• DDx “AFIP-CC”
•Amiodarone
•Fabry’s Dx.
•Indomethacin
•Plaquenil
•Chloroquine
•Chlorpromazine
4
Corneal Epithelium: Wound
Healing
Factors effective in wound healing:
„growth factors?
„fibronectin: from plasma and fresh wounds
„
effective in some PEDs but not others
„tretinoin: promotes proper differentiation of
proliferating epi cells
5
Corneal Epithelium: RES
2 Types
1. Primary
Corneal dystrophies.
2. Secondary
„ after minor trauma.
„ Most common reason for recurrent erosion syndrome
„ Usually lasts 8-12 weeks, but can be years
„ Cornea may be normal in between episodes
„ other: e.g., diabetes
6
Corneal Epithelium: Dystrophies
Map
Fingerprint
Dot
7
Corneal Epithelium: Dystrophies
Map-Dot-Fingerprint
„most common anterior corneal dystrophy
„3 main findings:
„ thickening of b.m. with extensions into epithelium
„ intraepithelial microcysts from degenerated, trapped epi
cells
„ fibrillar material between b.m. and underlying Bowman’s
„associated with recurrent erosions in 10%
„found in 50% of people with recurrent erosions
8
Corneal Epithelium: Dystrophies
Meesman’s Epithelial
Dystrophy
„autosomal dominant,
bilateral, seen in childhood
„multiple intraepithelial
vesicles
9
Corneal Epithelium: Dystrophies
Meesman’s Epithelial
Dystrophy
„asymptomatic until middle
age with irritation,
photophobia, RES
10
Corneal Epithelium: Dystrophies
Meesman’s Epithelial
Dystrophy
„histopath: thickened epi,
projections of b.m. into
epi, intracytoplasmic
fibrillogranular “peculiar
substance”
11
Corneal Epithelium: RES
Treatment
Medical
„ lubrication
„ hypertonic solutions
Surgical
„ anterior stromal micropuncture
„ superficial keratectomy
„ PTK
12
Stromal Dystrophies and Ectasias
1.
2.
3.
Anterior membrane dystrophies
Stromal dystrophies
Corneal ectasias
13
Anterior Membrane Dystrophies
„
„
„
Reis-Bücklers Dystrophy
Thiel-Behnke Honeycomb Dystrophy
Subepithelial Mucinous Corneal Dystrophy
Lot of confusion between first two.
14
Reis-Bücklers
Alternative Names
„ CDB I (Corneal Dystrophy of Bowman’s I)
„ SVGD (Superficial Variant of Granular
Dystrophy)
„ Granular dystrophy Type III
AD, 5q31 (BIGH3)
15
Reis-Bücklers
Clinical Features
„ RES beginning in first
few years of life
„ early and marked visual
loss (earlier than CDB
II)
„ superficial ring or mapshaped opacities
16
Reis-Bücklers
17
Reis-Bücklers
Pathology
„ subepithelial/anterior
stromal fibrosis
„ destruction of Bowman’s
„ Masson-positive granular
subepithelial deposits
(similar to granular
dystrophy)
„ Electron Microscopy: rodshaped bodies (similar to
granular dystrophy)
„
„
NOT “curly” fibers
“sawtooth” shape in region
of Bowman’s from scarring
18
Reis-Bücklers
Treatment
„ SK
„ PTK
„ Penetrating Keratoplasty
„
can recur in grafts
19
Thiel-Behnke
Alternative Names
„ CDB II (Corneal Dystrophy of Bowman’s II)
„ Honeycomb Dystrophy
AD, 5q31 (BIGH3)
20
Thiel-Behnke
Clinical Features
„ RES begins later in life,
in 1st/2nd decades
„ superficial reticular
corneal scarring
„ honeycomb or ringshaped opacities
21
Thiel-Behnke
Pathology
„ subepithelial/anterior
stromal fibrosis
„ destruction of Bowman’s
„ only equivocally positive
with Masson
„ Electron Microscopy: curly
fibers
„
“sawtooth” shape in region
of Bowman’s from scarring
(same as Reis-Bücklers)
22
Thiel-Behnke
Treatment
„ SK
„ PTK
„ Penetrating Keratoplasty
„
Can recur in grafts
23
Subepithelial Mucinous Corneal
Dystrophy
AD, very rare.
Clinical Features:
„RES in 1st decade of
life, subside over next
decade
„progressive visual loss
„dense, subepithelial,
gray-white patches
„ densest centrally
„intervening generalized
subepithelial haze to
limbus
24
Subepithelial Mucinous Corneal
Dystrophy
Pathology:
„eosinophilic, PAS +
subepithelial deposits
anterior to Bowman’s
„stain with Alcian Blue
„consist of chondroitin
sulfate and dermatan
sulfate
(mucopolysaccharides)
25
Subepithelial Mucinous Corneal
Dystrophy
Treatment
„ SK
„ Penetrating Keratoplasty
26
Stromal Dystrophies
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Lattice Dystrophy
Granular Dystrophy
Avellino Dystrophy
Macular Dystrophy
Gelatinous Drop-Like Dystrophy
Schnyder Crystalline Dystrophy
Central Cloudy Dystrophy of Francois
Fleck Dystrophy
Cornea Farinata
Pre-Descemet’s Dystrophy
Posterior Amorphous Corneal Dystrophy
Congenital Hereditary Stromal Dystrophy
Primary Band Keratopathy
27
Lattice Dystrophy
3 Types:
I: Primary corneal
II: Secondary, systemic
III, IIIA: Primary corneal
Types I, III: AD, 5q31 (BIGH3)
„ encodes for keratoepithelin, found in corneal
epithelial cells and stromal keratocytes
Type II: AD, 9q34
28
Lattice Dystrophies
Characteristic
Type I
Type II (Meretoja)
Type III
Inheritance
Autosomal dominant
Autosomal dominant
Autosomal
recessive?
Onset
<10 years
20 to 35 years
>40 years
Visual
acuity
Poor after age 40
Good until age 65
Impaired
after 60 yo
Erosions
Frequent
Infrequent
None
Cornea
Numerous, delicate lines, many
Few thick lines; periphery inamorphous deposits; periphery clear volved; few amorphous deposits
Thick
lines
Systemic
involvmnt
None
Amyloidosis involving skin,
arteries, and other organs
None
Face
Normal
Facial paresis and
blepharochalasis after age 40
Normal
29
Lattice Dystrophy Type I
Most common type.
Clinical Features:
„bilateral, may be
asymmetric
„fine, rod-like, glassy
opacities in anterior
stroma
„begin in 1st/2nd decade
„RES
„central anterior stromal
haze may develop
30
Lattice Dystrophy Type I
Pathology:
„amyloid deposits
„stain with Congo red,
PAS, and Masson’s
trichrome
31
Lattice Dystrophy Type I
Pathology:
„amyloid deposits
„stain with Congo red,
PAS, and Masson’s
trichrome
„dichroism and
birefringence seen with
polarized light
32
Lattice Dystrophy Type II
Secondary corneal amyloidosis.
„ associated with Meretoja syndrome
„ ie, Familial Amyloid Polyneuropathy Type IV
(Finnish type)
„ cranial neuropathy, including bilateral facial n.
„ systemic amyloid deposition
33
Lattice Dystrophy Type II
„lattice lines greater in
periphery
„fine lines, more radial
„clear intervening stroma
„RES less frequent
„visual changes less
severe
„higher incidence of
glaucoma and PXF
34
Lattice Dystrophy Type III
„thick, ropy lines
„no RES
„later in life (>40 yo)
„IIIA: French variant:
autosomal dominant,
with RES
Lattice Type IIIA
35
Granular Dystrophy
3 Types:
I: Classic granular dystrophy
II: Avellino dystrophy
III: Reis-Bücklers dystrophy
AD, 5q31 (BIGH3)
36
Granular Dystrophy Type I
AD, chrom. 5q (BIGH3)
„discrete corneal
opacities (breadcrumbs)
„whitish or glassy
„clear intervening stroma
„often asymptomatic
„RES in some (?SVGD)
37
Granular Dystrophy Type I
Pathology:
„stains red with Masson
trichrome
„EM: rod-like bodies
Treatment:
„PKP
„recurs superficially in
grafts
„can be treated with PTK
38
Avellino Dystrophy
„ autosomal dominant, chromosome 5q (BIGH3)
„ combines features of both granular and lattice
dystrophies
„ majority of patients from the Avellino region of
Italy
Clinical Features:
„ granular deposits in anterior stroma develop first
„ lattice lines deeper in the stroma develop later
„ gray, subepithelial haze centrally
„ RES
„ vision loss
39
Macular Dystrophy
Least common and most severe of the 3 classic
stromal dystrophies.
AR, 16q21.
3 Types:
I:
no detectable antigenic keratan sulfate (aKS) in
serum or cornea
II: normal amounts of aKS in serum and cornea
„ corneal deposits react with anti-KS antibody
IA: no detectable aKS in serum, but keratocytes react
with antibodies to keratan sulfate
40
Macular Dystrophy
Clinical Features:
„faint, white, anterior
stromal opacities early
in life
„become denser with
ground-glass haze
throughout anterior
stroma
„severe photophobia,
RES, and vision loss by
2nd to 3rd decades
41
Macular Dystrophy
Pathology:
„glycosaminoglycan
accumulation within and
outside keratocytes,
beneath epithelium, and
within endothelial cells
„stains with alcian blue,
colloidal iron, and PAS
Treatment:
„PKP: low recurrence in
grafts
42
Gelatinous Drop-Like Dystrophy
=Familial subepithelial amyloidosis.
Autosomal recessive, 1p.
Japan >> U.S., Africa, India.
Symptoms:
„ severe photophobia
„ tearing
„ decreased vision
43
Gelatinous Drop-Like Dystrophy
Clinical Features:
„gray/white/yellow
subepithelial nodules in
central cornea appear in
1st to 2nd decades
„become confluent over
time, giving mulberry
surface to cornea
„later: superficial
vascularization with
deeper amyloid
deposition
44
Gelatinous Drop-Like Dystrophy
Pathology:
„subepithelial and
anterior stromal
accumulation of
amyloid
Treatment:
„SK
„recurs in 2 years
„PKP
„early recurrences
45
Corneal Amyloidoses
46
Schnyder Crystalline Dystrophy
Autosomal dominant, variable
expressivity.
Associated with
hypercholesterolemia.
Clinical Features:
„ central subepithelial crystals
often in ring pattern
„ progresses to more diffuse
haze and arcus
„ diminished corneal
sensation
„ decreased vision after 4th
decade
47
Schnyder Crystalline Dystrophy
Pathology:
„oil-red O staining material (phospholipid,
cholesterol) throughout stroma, most
prominent
„ peripherally
„ in Bowman’s
„ just anterior to Descemet’s
„cholesterol clefts
Treatment:
„PKP
48
Central Cloudy Dystrophy of
Francois
Same appearance as
posterior crocodile
shagreen.
Autosomal dominant.
Pathology
„“sawtooth” disarray of
corneal stromal lamellae
49
Fleck Dystrophy
=speckle or Francois-Neeten
dystrophy.
Autosomal dominant.
Usually found incidentally.
Discrete, small, white,
comma-shaped opacities
scattered throughout all
levels of stroma.
No epithelial involvement.
Usually asymptomatic, but
may have photophobia.
50
Fleck Dystrophy
Pathology:
„distention of keratocytes
„vacuoles filled with lipid and acid MPS
„stains with oil-red O
Treatment not necessary.
51
Cornea Farinata
A degeneration (not a dystrophy).
Associated with aging.
Numerous, small, dust-like or flour-like
particles anterior to Descemet's membrane.
No clinical significance.
52
Pre-Descemet’s Dystrophy
Probably autosomal dominant or degenerative.
Bilateral, symmetric.
Onset after age 30.
Vision usually not affected.
53
Pre-Descemet’s Dystrophy
Clinical features:
„focal, fine gray dots in
posterior stroma
„variety of punctate and
linear shapes
„less commonly large
circular, comma,
boomerang, wormlike,
and dendritic shapes
„may be diffuse, central,
or form a ring
54
Pre-Descemet’s Dystrophy
Variant:
„punctiform and polychromatic pre-Descemet’s
dystrophy
Similar Entities
„polymorphic amyloid degeneration
„cornea farinata
„deep filiform dystrophy
Pre-Descemet’s opacities also seen in:
„pseudoxanthoma elasticum
„X-linked recessive ichthyosis
„keratoconus
55
Posterior Amorphous Corneal
Dystrophy
Rare, autosomal dominant, onset 1st decade.
Bilateral, symmetric, slow to not progressive.
Findings:
„ central and peripheral, deep, gray, broad
sheets of corneal opacification
„ some have only peripheral changes extending to
limbus
„ associated corneal flattening
„ central thinning (can be 300 microns)
„ iridocorneal adhesions have been reported
56
Posterior Amorphous Corneal
Dystrophy
Pathology:
„irregular disorganization of the corneal
lamellae anterior to Descemet's membrane
„lipid deposition within some keratocytes
Usually vision affected only minimally.
Treatment is unnecessary.
57
Congenital Hereditary Stromal
Dystrophy
Non-progressive, rare, autosomal dominant anomaly.
Clinical Features:
„bilateral, white, diffuse stromal clouding, most
prominent centrally
„absence of corneal edema, normal pachymetry and
IOP rule out glaucoma and CHED.
Pathology:
„separation of normal lamellae with loosely packed,
irregular layers of collagen
„thinner collagen fibrils (half of normal)
„lack of banding of anterior portion of Descemet’s
Treatment: PKP
58
Primary Band Keratopathy
Rare, autosomal recessive form of the normally
acquired band keratopathy seen in adults.
Presents in childhood.
59
Corneal Ectasias
1.
2.
3.
4.
Keratoconus
Pellucid Marginal Degeneration
Keratoglobus
Posterior Keratoconus
60
Keratoconus
Progressive corneal ectasia associated with corneal
thinning and usually inferior corneal steepening.
Probably autosomal dominant
„ one gene mapped to chromosome 21
„ family history in only 10%
Etiology unknown:
„ may be related to epithelial enzyme dysregulation.
Prevalence 1/2000 in general population.
Topographic signs seen in up to 5% of those seeking
refractive surgery for myopia.
61
Keratoconus
Clinical Features:
„ inferior corneal
steepening
„ Munson’s sign
„ Rizutti’s sign
„ Charleaux’s sign
„ Other signs
„ pulsation of mires on
tonometry or
keratometry secondary
to ocular pulse
transmitted through
thin cornea
62
Keratoconus
Clinical Features:
„ Fleischer ring
„ Vogt’s striae
„ apical thinning
„ protrusion at apex
„ hydrops
„ fibrosis
63
Keratoconus
Topographic Features:
„ inferior corneal
steeping
„ paracentral anterior &
posterior corneal
elevation
„ thinning corresponding
to above region
„ oblique axis of
astigmatism
64
Keratoconus
Diagnosis:
Rabinowitz suggested following criteria:
„ keratometry > 47.20D
„ steepening of inferior cornea of >1.2D
compared to superior cornea
„ skewing of radial axis of astigmatism >21º
Sensitivity 98%, specificity 99.5%
65
Keratoconus
Ocular Associations:
„ Leber’s congenital amaurosis
„ retinitis pigmentosa
„ retinopathy of prematurity
Systemic Associations:
„ atopy
„ vernal keratoconjunctivitis
„ Down’s syndrome
„ eye rubbing
„ Marfan’s
„ Ehlers-Danlos
66
Keratoconus
Pathology:
„breaks in Bowman’s
„fibrosis extending into
stroma
„breaks in Descemet’s
with hydrops
„ inward curling of
Descemet’s
67
Keratoconus
Treatment:
„ spectacles
„ contact lens
„ penetrating keratoplasty
„ Urrets-Zavalia syndrome
„ epikeratoplasty
„ lamellar keratoplasty
68
Pellucid Marginal Degeneration
Bilateral, peripheral, usually
inferior corneal ectasia.
Inheritance unknown.
Thinning is inferior to apex of
cornea.
„ begins 1-2 mm from inferior
limbus
„ thin zone is 1-2 mm wide x
6-8 mm long
„ no iron line or striae
„ usually clear (“pellucid”)
„ may develop hydrops, which
may lead to scarring &
vessels
69
Pellucid Marginal Degeneration
Against the rule
astigmatism centrally.
With the rule astigmatism
inferiorly.
70
Pellucid Marginal Degeneration
Horizontal mires closer
together centrally.
Vertical mires closer
together inferiorly.
(egg-shaped)
71
Pellucid Marginal Degeneration
Classic bent bowtie on
topography.
72
Pellucid Marginal Degeneration
Treatment:
„ large or eccentric PKP
„ large LKP, possibly followed by PKP
Easy to differentiate from other peripheral
thinning disorders.
73
Pellucid marginal
degeneration
Terrien's marginal
degeneration
Mooren's ulcer
Furrow
degeneration
Second to fifth
decade
Usually middle-aged
to elderly
Adult to elderly
Elderly
Laterality Bilateral
Bilateral
Unilateral and
bilateral types
Bilateral
Sex
Male = female
Males predominate
Males more
common
Male =
female
Astigmatism
Common
Common
Sometimes
None
Thinning
Inferior band 1-2 mm Usually starts
wide
superiorly
Starts within lid
fissure
Occurs with
arcus
Inflammation
None
Occasionally
Typical; worse in
bilateral type
None
Epithelial None
defect
Usually none
Typical
None
Vascular- None
ization
Crosses area of
thinning
Peripheral edge of
thinning
None
Lipid
deposits
None
Common; central to
thinning
Not acutely
Corneal arcus
Perforation
Hydrops more
common
Unusual
Common in
bilateral type
Never
Age at
onset
74
Keratoglobus
Bilateral, usually nonprogressive or
minimally progressive corneal
ectasia.
May be part of autosomal recessive
syndromes:
„ Ehlers-Danlos Type VI
„ brittle cornea syndrome (blue
sclera, red hair)
75
Keratoglobus
Clinical Features:
„ diffuse thinning greatest
in periphery
„ may be associated with
scleral thinning
„ normal or slightly
increased corneal
diameter
76
Keratoglobus
Clinical Features:
„ no iron line
„ minimal if any corneal
scarring
„ less likely to develop
hydrops than in KCN
„ more likely to rupture
after minimal trauma
77
Keratoglobus
Treatment:
„ protect from trauma
„ epikeratoplasty
„ large LKP, possibly followed by PKP
„ large PKP
78
Posterior Keratoconus
Congenital corneal anomaly with
protrusion of posterior corneal
surface
„ usually localized region
Usually sporadic and unilateral.
„ probably a variant of anterior
segment dysgenesis
Clinical Features:
„ often stromal scarring anterior to
Descemet’s in area of protrusion
Treatment is usually not necessary.
79
Keratoconus
Pellucid marginal
degeneration
Keratoglobus
Posterior
Keratoconus
Frequency
Most
common
Less common
Rare
Least common
Laterality
Usually
bilateral
Bilateral
Bilateral
Usually unilateral
Age at
onset
Puberty
Age 20 to 40 years
Usually at
birth
Birth
Thinning
Inferior
paracentral
Inferior band 1 to 2
mm wide
Greatest in
periphery
Paracentral posterior
excavation
Protru- Thinnest at
sion
apex
Superior to band of
thinning
Generalized
Usually none
Iron
line
Fleischer
ring
Sometimes
None
Sometimes
Scarring
Common
Only after hydrops
Mild
Common
Striae
Common
Sometimes
Sometimes
None
80
Corneal Endothelium: Anatomy
Endothelial cells
„ 3500-4000 cells/mm2 at birth, declines by 0.5%/yr. to 2600
„ 75% hexagonal early in life, decreasing to 60%
Descemet’s membrane
„ banded layer secreted in utero
„ starts 3um thick, banded
„ ends 10um thick, anterior banded, posterior not banded
81
Corneal Endothelium: Physiology
Maintenance of stromal deturgescence:
„ passive gradient of flow from hypo-osmotic cornea
to hyperosmotic aqueous
„ endothelial cells function to pump fluid out of
stroma and into aqueous via 2 mechanisms:
„ Na+, K+, -ATPase: membrane-bound
„ carbonic anhydrase: intracellular
82
Corneal Endothelial Injury
Endothelial stressors:
„ metabolic: hypoxia, hyperglycemia
„ toxic: drugs, preservatives
„ alterations in pH, ionization, or osmolarity
„ trauma from surgery
Changes to endothelium can appear locally, and
therefore not seen on randomly selected specular
microscopy photographs.
83
Corneal Endothelial Injury
Hypoxia:
„ contact lens wear
possible permanent
changes to endothelium
„ variation in cell size
increases
„ percentage of hexagonal
cells decreases
„
84
Corneal Endothelial Injury
Hyperglycemia:
„ changes in endothelium
compared to agematched controls
variation in cell size
increases
„ percentage of hexagonal
cells decreases
„
„ doesn’t appear to affect
function clinically
85
Endothelial Disorders
„ Fuchs’ dystrophy
„ CHED—congenital hereditary endothelial dystrophy
„ PPMD—posterior polymorphous dystrophy
„ Endothelial trauma
86
Endothelial Disorders: Fuchs’
Epidemiology
„ most common corneal dystrophy requiring
transplantation
„ autosomal dominant with variable expressivity
„ female:male 4:1
„ Caucasian=African-American>Asians
„ symptoms in middle age
87
Endothelial Disorders: Fuchs’
Pathogenesis
„ altered Na+,K+-ATPase pump activity
„ normal barrier function
88
Endothelial Disorders: Fuchs’
Guttae:
„ excrescences of Descemet’s
membrane
„ not pathognomonic for
Fuchs’
„
„
„
11% of people over 50yo have
guttae
seen in other conditions,
including uveitis
pathologically identical to
Hassall-Henle bodies seen in
periphery
89
Endothelial Disorders: Fuchs’
Guttae:
„ start discretely in center,
advance to periphery and
coalesce (“beaten metal”)
90
Endothelial Disorders: Fuchs’
Staging
Endothelial changes only, vision not affected
1.
Stromal swelling, especially in mornings, with
2.
affected vision.
Progressive stromal and epithelial microcystic
3.
edema, recurrent erosions, pannus formation,
anterior stromal haze.
91
Endothelial Disorders: Fuchs’
Exam
„ Specular microscopy
„ Sclerotic scatter
„ Pachymetry
„ Retro-illumination
92
Endothelial Disorders: Fuchs’
Pathology:
„ guttae
„ thickened, abnormal
Descemet’s
„
„
abnormal posterior banded
layer
fibrillar layer
„ Descemet’s changes can be
seen before guttae
„ paucity of endothelial cells
93
Endothelial Disorders: CHED
One of the many causes of bilateral congenital corneal
clouding.
„ Inheritance: AD, AR, or sporadic
„ corneal thickness two to three times the normal
„ normal IOP
„ normal horizontal corneal diameter
„ associated features: corneal pannus, nystagmus,
esotropia
„ usually requires penetrating keratoplasty
94
Endothelial Disorders: CHED
Onset:
„ corneal clouding may be maximal at birth or progress
over a period of years
„
CHED 1: AD inheritance: progressive onset of corneal
edema 1-2 years postpartum with associated photophobia,
but without nystagmus
„
„
Genetic locus 20p11.2 – q11.2
CHED 2: AR inheritance: presence at birth of bilateral
corneal edema without photophobia, but with nystagmus
„
Genetic locus 20p13
95
Endothelial Disorders: CHED
Pathogenesis
„ abnormal neural crest cell terminal induction during
the late term to perinatal period
„ failure to complete final differentiation of the
endothelial monolayer
„ results in a dysfunctional endothelium with faulty
growth regulation mechanisms
„ leads to formation of abnormal, thickened posterior
nonbanded Descemet's membrane
96
Endothelial Disorders: CHED
Findings
„ diffuse stromal gray-blue ground-glass coloring
„
„
uniform density anterior to posterior within a given region
variable density across cornea
„ where stromal opacification is less dense, Descemet's
membrane appears gray and on specular reflection may have a
'peau d'orange' texture
„ irregular texture of epithelial surface with diffuse “pigskinlike” roughness
„
recurrent epithelial erosions are uncommon
„ discrete white dots may be seen in the stroma
„ fine corneal pannus may be seen
97
Endothelial Disorders: CHED
Prognosis
„ usually requrire penetrating keratoplasty
„ 5-year graft survival rate about 50%
„ usually left with haze/opaque grafts
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Endothelial Disorders: PPMD
Definition
„ rare, bilateral, usually autosomal dominant with
variable penetrance, cases of autosomal recessive
„ polymorphic posterior corneal surface irregularities
„ widely variable degrees of corneal decompensation
„
„
majority of patients are asymptomatic with subtle findings
can present with congenital corneal clouding
Genetic locus:
PPCD1 – 20p11.2-q11.2
PPCD2 – 10p11.2
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Endothelial Disorders: PPMD
3 types of endothelial changes:
„ vesicles
„ 0.2-1 mm diameter
„
curvilinear irregularities
„ band-shaped or snail track areas
with scalloped edges, 1mm wide,
2-10 mm long
„
placoid irregularities
„ rare, diffuse corneal presentation
„ hazy Descemet’s and posterior
stroma
„ assoc. with corneal edema and
iridocorneal adhesions
Usually normal vision in vesicular &
curvilinear, compromised in
placoid.
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Endothelial Disorders: PPMD
Other Features:
„ endothelial changes best seen in
retroillumination with dilated
pupil
„ rounded dark areas with cells that
give a doughnut-like pattern on
specular microscopy
„ reduced endothelial cell counts
„ iridocorneal adhesions, peripheral
anterior synechiae, & glaucoma
most commonly in placoid type
„ tendency to recur in grafts
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Endothelial Disorders: PPMD
Pathogenesis
„ focal transformation of endothelial cells into
fibroblast-like and epithelial-like cells
„ transformation of endothelial monolayer into
multilayer epithelium-like tissue
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Endothelial Disorders: PPMD
Pathology
„ pits of the posterior corneal
surface which correspond to
the vesicles seen on exam
„ attenuated Descemet's
membrane in these areas
„ multilayered endothelium
„ in other areas, Descemet's
membrane appears
multilayered, of variable
thickness, and with
attenuation or loss of
endothelium
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Endothelial Disorders: PPMD
Pathology
„ features of abnormal
endothelial cells:
„ surface microvilli
„ multilayered
„ contain numerous
desmosomes and
intracytoplasmic filaments
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Endothelial Disorders: PPMD
Course
„ believed to be nonprogressive
„ usually without vision impairment
„ penetrating keratoplasty for those with vision
impairment
„ risk for recurrence in the grafted cornea
„ risk for development of severe post-transplant glaucoma
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Endothelial Disorders: Trauma
Blunt trauma: 2 mechanisms of injury
1. Mechanical deformation of cornea
„ buckling of cornea from blunt or surgical trauma
„ causes annular endothelial
stress with focal destruction of
cells
„ grayish swelling of endotheial cells gives “snail track”
appearance and dark spots at level of Descemet’s
„ dark spots may resemble guttae, but are more regular in
size, not pigmented, and are reversible
„ surrounding cells migrate rapidly
„ usually no changes evident beyond 1-3 days
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Endothelial Disorders: Trauma
Blunt trauma: 2 mechanisms of injury
2. Rupture of Descemet’s membrane
„ severe blunt trauma, forceps delivery
„ Descemet’s curls in toward stroma
„ causes acute hydrops
„ surrounding cells migrate and produce new Descemet’s
„ corneal edema resolves as new endothelial cells fill in
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Isolated Congenital Corneal
Anomalies
1.
Anomalies of corneal size:
a.
b.
c.
2.
microcornea
megalocornea
congenital corneal ectasia
Anomalies of corneal clarity
a.
b.
c.
d.
e.
anterior embryotoxon
posterior embryotoxon
corneal keloids
Peters’ anomaly
sclerocornea
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Isolated Congenital Corneal
Anomalies of Size
Normal horizontal corneal diameter:
„
„
9.5-10 mm at birth
10-12.5 mm in adulthood
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Isolated Congenital Corneal
Anomalies of Size
Microcornea:
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Isolated Congenital Corneal
Anomalies of Size
Microcornea:
„
„
„
„
„
HCD <9 mm at birth, <10 mm in adult
mostly sporadic
some autosomal recessive and dominant (autosomal
dominant assoc. with cataract and anterior segment
anomalies)
remainder of eye normal, unlike microphthalmos
can lead to angle closure glaucoma as lens enlarges
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Isolated Congenital Corneal
Anomalies of Size
Megalocornea:
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Isolated Congenital Corneal
Anomalies of Size
Megalocornea:
„ HCD >12 mm at birth, >13 mm after 2 years of age
„ bilateral anterior segment enlargement
„ IOP and overall globe size normal, unlike buphthalmos
and megalophthalmos
„ usually myopic
„ Genetic forms:
„ X-linked
recessive: more common, associated with TIDs, pigment
dispersion, lens subluxation, arcus, & central crocodile shagreen;
normal endothelial cell density, corneal thickness, and clarity
„ autosomal dominant least common, no other ocular abnormalities
„ other forms associated with congenital miosis, ectopia lentis et
pupillae, and mental retardation
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Isolated Congenital Corneal
Anomalies of Size
Congenital Corneal Ectasia:
= congenital anterior staphyloma
„ often seen with Peters’ anomaly
„ marked corneal thinning and
bulging (worse than in usual
Peters’ cases)
„ usually unilateral
„ often associated with iris
developmental defects
„ etio: inflammatory or infectious
corneal thinning in utero?
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Isolated Congenital Corneal
Anomalies of Clarity
Developmental Correlate:
„ lens vesicle separates from surface ectoderm at 5th week
gestation
„ mesenchymal neural crest cells migrate between surface
ectoderm and optic cup in 3 waves
„
„
„
1st wave: corneal endothelium, trabecular meshwork
2nd wave: stromal keratocytes
3rd wave: anterior iris stroma
separation of these waves of cells forms the anterior chamber
„ alterations in these steps leads to abnormalities of specified
structures
„
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Isolated Congenital Corneal
Anomalies of Clarity
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Isolated Congenital Corneal
Anomalies of Clarity
Anterior Embryotoxon
„ term used to describe a congenital broad limbus
superiorly with an otherwise normal anterior segment
„ merely represents a broad transition from sclera to
cornea
„ also used to describe an appearance similar to arcus
senilis (arcus juvenilis) present at birth
„ often sporadic, some autosomal dominant and
autosomal recessive
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Isolated Congenital Corneal
Anomalies of Clarity
Posterior Embryotoxon
„ most
frequently seen isolated
corneal anomaly
„ thickening and anterior
displacement of Schwalbe's line
„ most easily seen in the temporal
cornea
„ “toxon” derived from the Greek
word for bow, referring to the
crescent of Schwalbe's line
„ no clinical significance when
present in isolation
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Isolated Congenital Corneal
Anomalies of Clarity
Corneal Keloids
„
„
„
„
„
„
„
„
white, glistening, protuberant lesions that involve all or part of the cornea
usually acquired from trauma or ocular inflammation
congenital variant exists, usually bilateral
histopathology: hypertrophic scar with irregularly arrayed collagen
bundles, fibroblasts, and capillaries arising in the corneal stroma
may be progressive
sometimes associated with disorders that involve oculodigital
manipulation (e.g. Lowe's syndrome)
treatment: keratoplasty if no other ocular abnormalities
if other abnormalities, consider dissection of the lesion from the cornea
followed by covering with a conjunctival flap to halt progression
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Isolated Congenital Corneal
Anomalies of Clarity
Peters’ Anomaly
„ Type
I: “Primary”
„ usually unilateral
„ central or paracentral corneal
opacity with iris strands attaching
to the periphery of the opacity
„ a defect in corneal endothelium and
Descemet's membrane is present
initially, often with marked corneal
edema that can extend well beyond
the defect
„ over time the surrounding
endothelium covers the defect,
produces new basement
membrane, and the edema
regresses to leave the corneal
opacity only
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Isolated Congenital Corneal
Anomalies of Clarity
Peters’ Anomaly
„ Type II: “Secondary”
„ usually
bilateral
„ lens involvement: lens
adherence to the posterior
cornea, failure of complete
separation of the lens from the
cornea, and/or cataract
„ usually other ocular associations
„ usually other systemic
associations (can be severe)
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Isolated Congenital Corneal
Anomalies of Clarity
Peters’ Anomaly
„
„
ocular associations: include chorioretinal coloboma, iris coloboma, PHPV,
microphthalmos, and optic nerve hypoplasia
systemic associations:
„
„
„
„
Krause-Kivlin syndrome: short stature, facial dysmorphism, developmental
delay, and delayed skeletal maturation; autosomal recessive
Peters'-plus syndrome: Peters' anomaly with syndactyly, genitourinary
anomalies, brachycephaly, central nervous system anomalies, cardiac disease, or
deafness; FOXC1?
fetal alcohol syndrome
posterior keratoconus and posterior ulcer of von Hippel might be thought
of as Peters' anomaly without iris adhesions
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Isolated Congenital Corneal
Anomalies of Clarity
Peters’ Anomaly
„
Pathology
„
„
„
„
„
absence of Descemet's membrane and endothelium in the area of
opacity initially
endothelial cells and Descemet's membrane defects are replaced by
surrounding cells
residual fibrosis in the posterior stroma
usually absent central Bowman's membrane
Treatment
„
„
„
treat associated glaucoma
penetrating keratoplasty for bilateral corneal opacification
visual outcomes often are not ideal
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Isolated Congenital Corneal
Anomalies of Clarity
Sclerocornea
scleral-like clouding of cornea
„ can be peripheral or diffuse
„ may be associated with cornea plana (flat cornea)
„ may be associated with most other anterior segment
anomalies
„ glaucoma is common
„ usually sporadic, bilateral
„
„
X-linked form: microphthalmia, dermal aplasia, sclerocornea
treat: control glaucoma; penetrating keratoplasty
„ poor outcomes often secondary to severe glaucoma
„
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