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Via Paccagnella 11
30174 Zelarino-VENEZIA
(ITALY)
DYSTROPHY
DEGENERATION
Dystrophy
(Fuchs)
Degeneration
Dystrophy
DYSTROPHY
UNILATERAL
BILATERAL
DYSTROPHY
ASYMMETRIC
SYMMETRIC
DYSTROPHY
POSTOPERATIVE
SPONTANEOUS
DYSTROPHY
PERIPHERAL
CENTRAL
(usually)
(usually)
DYSTROPHY
VASCULARIZED
AVASCULAR
DYSTROPHY
LATE ONSET
EARLY ONSET
QUICK
PROGRESSION
DYSTROPHY
SLOW
PROGRESSION
DYSTROPHY
SECONDARY
PRIMARY
DYSTROPHY
NON HEREDITARY
HEREDITARY
(Autosom. Dom.)
CORNEAL DYSTROPHIES
CLASSIC MORPHOLOGIC
(ANATOMIC) CLASSIFICATION
Epithelium (e.g. map-dot-fingerprint)
Bowmans Layer (e.g. Reis-Bckler)
Stroma - Deposition (e.g. Graenouw)
Stroma - Ectasia (e.g. Keratoconus)
Endothelium (e.g. guttata, Fuchs)
epithelial
basement
membrane
dystrophy.
Retroillumination of
highlighted basement
membrane dystrophy seen
as fingerprint lines and map
patterns.
intraepithelial microcyst
(Cogan)
Meesmann Dystrophy
Retroillumination
Meesmann Dystrophy
Microvacuoles in
retroillumination.
These are fine vacuola
changes in the
epithelium
Intraepithelial cysts
Thickening of
epithelial basement
membrane
Meesmann Dystrophy
Reis-Bckler Dystrophy
AD, chromosome 5q31 (same
as granular,
lattice, and Avellino)
Onset in second decade
Recurrent erosions, decreased
VA (anterior scarring)
Gray-white, fine, round
central opacities in
Bowmans layer,
Reis-Bckler Dystrophy
Progresses with age
Laying down of irregular
bands of collagen
replacing Bowmans
layer
Sawtooth fashion,
corresponding to
subepithelial opacities
Reis-Bckler Dystrophy
Rodlike
granules, seen
by transmission
electron
microscopy in
the superficial
stroma and in
the region of
Bowmans layer,
Reis-Bckler Dystrophy
TREATMENT:
Superficial keratectomy ?
Lamellar keratoplasty ?
PTK ???
Rarely PK
Recurrence in the graft (interface for LK) is very
common
Reis-Bckler Dystrophy
Recurrence 2
years after
excimer laser
ablation (area
of treatment !!!)
Thiel-Behnke Dystrophy
Thiel-Behnke Dystrophy
Curly filaments
(TEM) in the
region of
Bowmans
layer
Thiel-Behnke Dystrophy
Several years after
corneal
transplantation there
is recurrence of the
pathology in the
region of Bowmans
layer and superficial
cornea.
Thiel-Behnke Dystrophy
Thiel-Behnke
Dystrophy
pre-SALK
Thiel-Behnke
Dystrophy
post-SALK
Lattice Dystrophy
(Haab-Dimmer)
AD, chromosome 5q31:
Linear amyloid deposits
concentrated in anterior
stroma and subepithelial
areas
Stains orange-red with
Congo Red dye
Lattice Dystrophy
(Haab-Dimmer)
Refractile lines, or lattice
lines, best seen on
retroillumination
Central and subepithelial
white dots
Diffuse anterior stromal
haze
Clear cornea inbetween lines
Lattice Dystrophy
(Haab-Dimmer)
Classic lattice dystrophy
Chromosome 5q31
Onset at end of first decade
with recurrent erosions
preceding stromal changes
Treatment: PK or DALK
usually needed by sixth
decade
Lattice Dystrophy
(Haab-Dimmer)
Lattice Dystrophy
(Meretoja Syndrome)
Associated with systemic
amyloidosis
Chromosome 9q34
Onset third decade with
recurrent erosions
More delicate, sparse,
radially oriented
lattice lines
Lattice Dystrophy
(Meretoja Syndrome)
Systemic features:
progressive B cranial and
peripheral neuropathy
dysarthia
dry and lax itchy skin, mask
like facies
protruding lips
pendulous ears
Granular Dystrophy
AD, chromosome 5q31
Corneal stroma clear
inbetween opacities
Granular Dystrophy
See sharply demarcated
deposits resemblingcrumbs
or snowflakes in the central
anterior stroma, often
distributed in a radial
fashion
In time, number, size, and
depth of deposits increases
with gradual confluence and
diffuse opacity
Granular Dystrophy
Treatment: PK or DALK by age
40-50
Recurrences frequent
DO NOT treat
with excimer laser !!!
Histology shows amorphous
hyaline deposits that stain red
with Masson trichome
Granular Dystrophy
(Type II Avellino)
Combination of
patterns (bread
crumbs more
superficial, snow
flakes deeper)
MK-ASSISTED ANTERIOR LK
COMPLICATIONS
Dystrophy Recurrence
4/23 (17%)
Pre-SALK
Post-SALK
4-years
Post-SALK
DYSTROPHY RECURRENCE
Superficial
Recipient
Stroma
!!!
(Intracorneal)
DYSTROPHY RECURRENCE
HISTOLOGY OF RECURRENCE
PAS
Trichrome Masson
Macular Dystrophy
Macular Dystrophy
Deep
Periferal
Lesions
Type I
more prevalent
normal synthesis of dermatan sulfateproteoglycan
Erroneous synthesis of keratan sulfate
Type II
normal ratio of keratan sulfate and
dermatan sulfate but
decresed overall synthesis
Tratment: Treat recurrent erosions,
PK
Recurrence relatively rare
Central Cristalline
Deposit
Fuchs Dystrophy
Very common
May be AD but genetics
not cleared yet
Female preponderance
Onset after age 50
Ranges from
asymptomatic guttata to
a decompensated cornea
(Bullae)
Fuchs Dystrophy
Corneal guttae
with melanin
granule
pigmentation
Pathogenesis: reduction
in Na, K-ATPase pump
sites and/or function
Increased corneal edema
and deposition of
collagen and
extracellular matrix in
Descemets membrane
Fuchs Dystrophy
Stage 1: gradual increase in
cornea guttata with
peripheral spread - beaten
metal
Stage 2: endothelial
decompensation leading to
stromal edema and blurred
vision, initially worse when
waking up
Fuchs Dystrophy
Stage 3: Persistent
epithelial edema
leading to microcysts
and bullae which
cause pain upon
rupture
Fuchs Dystrophy
Check pachymetry and specular
microscopy (peripheral cell count !!!)
TREATMENT:
Reduce edema with NaCl drops
Lower IOP ??? (ridiculous !!!)
BCL to enhance evaporation
In the past PK- NOW DSAEK
Posterior Polymorphous
Dystrophy (PPD)
Uncommon, slowly
progressive
AD (AR), Chromosome 20q11
Onset birth or soon thereafter
Areas with endothelial cells
that behave like epithelial
cells (microvilli)
Posterior Polymorphous
Dystrophy (PPD)
These cells
show microvilli
stain positive for keratin
rapidly grow
have intracellular
desmosomes
Descemets membrane is
thickened
Diffuse
Opacities
Linear Band
Lesion
DSAEK in PPD
PPD (Age=12)
BSCVA = 1/10
Ref. = +2.00 sph.
1 y. post-DSAEK
BSCVA = 10/10
Ref. = +1.00 sph.
-0.75 cyl. @ 170
(Dominant)
Early Onset
Bilateral Clouding
Amblyogenic
NORMAL ANATOMY !!!
DSAEK in CHED
3 y post-DSAEK
BSCVA = 8/10
Ref. = +2.25 sph.
-2.25 cyl. @ 150
EDTA ABRASION
(with normal endothelium!)
MAP-DOT-FINGERPRINT
EPITHELIAL DEBRIDEMENT
(PTK)
CAVE !!!
EXTREME PMCD
79y, Low Vision Since
Years
270 Advanced Peripheral
Thinning with Ectasia
Normal
Thinning
HYDROPS IN PMD
Thinning
Normal
Rare
Descemets Break in the Area of Superior
Thinning
Aqueous Influx into Corneal Stroma
Treatment
Peripheral Corneal Tuck !!!
No
Results #1
Ectasia
BSCVA=0,4
(-4,00 cyl.@100)
Results #2
Day 1
Postop
No
Ectasia
No
Edema
BSCVA=0,6
Keratoconus
CAVE !!!
KERATOCONUS
High K-Readings
Asymmetry
KERATOCONUS
KC fruste
or
Astigmatism
???
KERATOCONUS
KC Fruste Preop
or
post-LASIK Ectasia
???
Fleischer
Ring !!
!
KERATOCONUS
38-Year Old Patient s/p ICRS x KC
Preop Refraction = -8,50 sph. -7,00 cyl. @ 180
KERATOCONUS
17-Year Old Patient s/p RK x KC !!!
Preop Refraction = - 1,00 sph. - 1,75 cyl. @ 175
Post-RK Refraction = + 1,00 sph. -1,50 cyl. @ 170
CORNEAL DYSTROPHIES
CLASSIC MORPHOLOGIC
(ANATOMIC) CLASSIFICATION
Epithelium (e.g. map-dot-fingerprint)
Bowmans Layer (e.g. Reis-Bckler)
Stroma - Deposition (e.g. Graenouw)
Stroma - Ectasia (e.g. Keratoconus)
Endothelium (e.g. guttata, Fuchs)
IC D
3
International Committee on
Classification of Corneal Dystrophies
Sponsored by The CORNEA Society
2008
CORNEAL DYSTROPHIES
NEW IC3D CLASSIFICATION
Morphologic (Anatomic)
Evidence Categories (1 to 4)
Dystrophies with common
genetics grouped together
CORNEAL DYSTROPHIES
EVIDENCE CATEGORIES
1. Well-Defined
Dystrophy
Known
Location,
Gene &
Mutation
CORNEAL DYSTROPHIES
EVIDENCE CATEGORIES
2. Well-Defined
Dystrophy
Known
Location
(Gene?)
CORNEAL DYSTROPHIES
EVIDENCE CATEGORIES
3. Well-Defined
Dystrophy
No Known
Genetics
CORNEAL DYSTROPHIES
EVIDENCE CATEGORIES
4. Suspected
New or Query
Distinct
Dystrophy
CORNEAL DYSTROPHIES
CORNEAL DYSTROPHIES
CORNEAL DYSTROPHIES
Beta-Transforming Growth
Factor Induced Gene Human
Clone
(BigH3 or Keratoepithelin)
(Chromosome 5q31)
CORNEAL DYSTROPHIES
BigH3 (Keratoepithelin)
CORNEAL DYSTROPHIES
Non - BigH3
CORNEAL DYSTROPHIES
WHY IDENTIFY RESPONSIBLE
GENES ???
To develop specific diagnostic tests
(similar disorders, clinical course)
To develop experimental models
To develop genetic treatments
(pharma, gene replacement, gene
suppression)
CORNEAL DYSTROPHIES
GENETIC TREATMENT
Delivery of Recombinant Genes
(Transgenes) to Corneal Tissue
Efficiency of Transgene Delivery
Duration of Transgene Activity
Safety
!!!
CORNEAL DYSTROPHIES
GENETIC TREATMENT
vs
CONVENTIONAL
TREATMENT
(SURGERY)
CORNEAL DYSTROPHIES
PENETRATING KERATOPLASTY
CORNEAL DYSTROPHIES
???
PETERS
ANOMALY
Congenital
Sporadic
Stable
CORNEAL EMBROLOGY
VI Week:
The Optic Cup
Reaches the
Crystalline
Lens
CORNEAL EMBROLOGY
3 Waves of
Undifferentiated
Ectodermic
Tissue
1st = Endothelium
2nd = Stroma
CORNEAL EMBROLOGY
Stepladder
Classification
Waring
1975
CONGENITAL
Anomalies Syndromes
Only
Ocular
Ocular +
Systemic
(Glaucoma)
CONGENITAL ANOMALIES
CONGENITAL ANOMALIES
Embriotoxon
CONGENITAL ANOMALIES
Axenfeld
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Rieger
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Keratoconus
Posticus
CONGENITAL ANOMALIES
Keratoconus Posticus
Normal
Endothelium (
2
1900 cell/mm )
VA = 20/20
CONGENITAL ANOMALIES
Peters I
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Peters II
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Peters II
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Peters II
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Peters II
Anomaly
(Syndrome)
CONGENITAL ANOMALIES
Microcornea
(Nanophthalmos)
(Microphthalmos)
CONGENITAL ANOMALIES
Megalocornea
CONGENITAL ANOMALIES
Buphthalmos
Haab
Striae
MYTH # 6:
CORNEAL NEOVESSELS
Infections
Chronic
Inflammation
(BK, Loose
Sutures, CL
wear, etc.)
CLINICAL CASE
85-Year-Old Woman, No Surgery
VA = LP
Diffuse Pannus
5-Year History
Ulcer
Inflammation +
CLINICAL CASE
85-Year-Old Woman, No Surgery
Other Eye
Relatively
Normal
Small Pannus
Good VA (0.6)
CLINICAL CASE
85-Year-Old Woman, Rosacea
Treat Rosacea!!!
Systemic & Topical
TETRACYCLINES
Topical
STEROIDS
CLINICAL CASE
5 Years Mushroom PK
CONGENITAL SCD
ANIRIDIA
Hereditary
(PAX6)
Sporadic
(Wilms Tumor)
CONGENITAL SCD
PAX6 = SCD
IRIS MAY
BE
NORMAL !!!
ACQUIRED SCD
CHEMICAL
TRAUMAS
(alkali, acids,
etc.)
ACQUIRED SCD
AUTOTRANSPLANT
IN UNILATERAL
LESIONS:
Thoft
1977
Herman
1983
Kenyon
1989
Busin
1994
ACQUIRED SCD
ACQUIRED SCD
AUTOTRANSPLANTATION
DAY 1
ACQUIRED SCD
AUTOTRANSPLANTATION
MONTH 1
ACQUIRED SCD
AUTOTRANSPLANTATION
PREOP
VA = LP
Month 1
VA = HM
Month 4
VA = 0.1
ACQUIRED SCD
AUTOTRANSPLANTATION
ACQUIRED SCD
AUTOTRANSPLANTATION
PREOP
VA = LP
Month 1
VA = 0.2
Month 4
VA = 0.4
ACQUIRED SCD
AUTOTRANSPLANTATION
PREOP
VA = LP
Year 1
VA = 0.4
ACQUIRED SCD
AUTOTRANSPLANTATION
PREOP
VA = LP
Year 1
VA = 0.1
ACQUIRED SCD
AUTOTRANSPLANTATION
PREOP
VA = LP
Year 1 1/2
VA = 20/200
ACQUIRED SCD
BILATERAL LESIONS
RECOVERY FROM
DONOR
TRANSPLANTATION
SURVIVAL ???
CORNEAL DISEASES
ULTIMATE MYTH:
PERFECT VISION IS THE GOAL
CORNEAL DISEASES
ULTIMATE FACT:
COMPROMISE MAY BE BETTER
BREAK !!
!