CORNEAL DYSTROPHY

Dr.RAJARATHNA THANGAVEL

CORNEA - ANATOMY

• Tear film 7-11 um• Epithelium 50 um • Epithelial BM <128 nm• Bowman 8-14 um• Stroma 500 um • Descemet 5-10 um• Endothelium 5 um

DYSTROPHY - Definition

• Greek Dys – wrong; Trophe – nourishment• Bilateral • Symmetric• Inherited condition• Little or no relationship to environmental or systemic

factors• Begin in early life but may not become clinically

apparent until later• Slowly progressive• Absence of inflammation

GOALS OF EXAMINATION

• Make a diagnosis• Manage patients to maximize– Comfort– Vision

STEPS IN DIAGNOSIS

• Structured Approach• Careful family history• Differentiate it from corneal degeneration• Recognise the pattern of the lesions

“Genotypes need phenotypes”• Examine the depth of the lesions• Assess severity and stage of the dystrophy• Genetic analysis• HPE

SLIT-LAMP EVALUATION of CD

Precise rules:• Examination of both eyes• Examination with dilated pupils

– Direct and Retro illumination• Topographical determination of lesion

– Superficial– Stromal– Endothelial– Combination

• Characteristic opacity pattern in direct illumination• Characteristic opacity units in direct and indirect illumination• Pseudoinflammatory signs• CORNEA DIAGRAM

SLIT LAMP ILLUMINATION TECHNIQUESDIRECT FOCAL SCLEROTIC SCATTER

INDIRECT ILLUINATION

OPTICAL SECTION OF CORNEA

CLASSIFICATION OF CD

Anatomic classification:• Anterior corneal dystrophies : Epithelium and

its basement membrane or Bowman layer and the superficial corneal stroma

• Stromal corneal dystrophies: Stroma

• Posterior corneal dystrophies: Descemet membrane and endothelium

IC3D CLASSIFICATION

• Traditional classification• Genetic• Clinical• Pathologic information

EPITHELIAL AND SUBEPITHELIAL DYSTROPHIES

EPITHELIAL DYSTROPHIES

Epithelial basement membrane dystrophy

Epithelial recurrent erosion dystrophy

Subepithelial mucinous corneal dystrophy

Meesmann corneal dystrophy

Lisch epithelial corneal dystrophy

Gelatinous drop-like corneal dystrophy

EPITHELIUM• 50 um non-keratinized stratified squamous epithelium• Central: 5-10 layers• Peripheral: 8-10 layers• Superficial layers - microvilli • Exfoliation: 5-7 days• Basal columnar cells - Hemi-desmosomes

Epithelium ―HD― basement membrane -Bowman’s Layer

MEESMANN’S

• D/d: microcystic edema due to contact lens wear

• Prognosis: good

• When to treat?– Symptomatic (due to rupture of cysts)– Scarring after rupture

• How to treat?

EPITHELIAL BASEMENT MEMBRANE DYSTROPHY (EBMD)

• Thickened basement membrane• Abnormality of epithelial turnover,

maturation, and production of BM and adhesion complexes

Morphology of lesions:

MAPS - Geographic epithelial changes

DOTS - opaque irregular opacities

FINGERPRINTS - concentric irregular lines

• Recurrent corneal erosions

• LASIK - absolute contraindication

How to manage EBMD patients?• Asymptomatic and mild: Regular follow-up• Recurrent corneal erosions:– Hypertonic saline ointment– Bandage contact lens– Epithelial debridementPersistent lesions– Anterior Stromal Puncture– PTK

• Decreased visual function– PTK

GELATINOUS DROP-LIKE CORNEAL DYSTROPHY

• Small multiple nodules – “mulberry “• Deep lamellar keratoplasty• PTK -To remove corneal opacities that recur

after lamellar grafts

BOWMAN’S LAYER DYSTROPHIES

1. Reis-Buckler’s

2. Thiel-Behnke’s

3. Grayson –Wilbrandt’s

BOWMAN’S LAYER

• Acellular modified layer of anterior stroma

• Randomly arranged Type 1 collagen fibers

• Pores for corneal nerves

• Not regenerated after damage

REIS-BUCKLER’s DYSTROPHY

THIEL-BEHNKE DYSTROPHY

STROMAL DYSTROPHIES

1. Lattice corneal dystrophy2. Granular Corneal dystrophy3. Macular corneal dystrophy4. Schnyder corneal dystrophy5. Congenital stromal corneal dystrophy6. Fleck corneal dystrophy 7. Posterior amorphous corneal dystrophy8. Central cloudy dystrophy of Francois9. Pre-Descemet corneal dystrophy

GRANULAR DYSTROPHY

MACULAR DYSTROPHY

LATTICE DYSTROPHY

• LCD type I:– classic form of LCD– BIGH3 gene mutation– Isolated amyloid deposition

in the cornea

LCD type II (Meretoja syndrome)• Systemic amyloidosis - skin, cranial nerves and

cornea• Gelsolin gene

• LCD types III and IIIA present later in life with thicker linear opacities in the mid corneal stroma

• LCD type III:– autosomal recessive– 7th-8th decade– No erosions

• LCD IIIA– autosomal dominant– BIGH3 mutation– 4th-5th decade– erosions and decreased vision

LCD type IV• Deep stroma• BIGH3 gene mutation

AVELLINO DYSTROPHY

SCHNYDER’S CENTRAL CRYSTALLINE DYSTROPHY

POSTERIOR AMORPHOUS DYSTROPHY

CONGENITAL HEREDITARY STROMAL DYSTROPHY

ENDOTHELIAL DYSTROPHIES

1. Fuchs endothelial corneal dystrophy

2. Posterior polymorphous corneal dystrophy

3. Congenital hereditary endothelial dystrophy

1 (CHED1)

4. Congenital hereditary endothelial dystrophy

2 (CHED2)

5. X-linked endothelial corneal dystrophy

(XECD)

SPECULAR REFLECTION

FUCH’S ENDOTHELIAL DYSTROPHY- Stage 1

GUTTATA• Clear, vesicular endothelial secretions• Project into the potential space between the endothelium and

Descemet’s

Stage 2

• Stromal edema

Stage 3

• Epithelial bullae

Stage 4

MANAGEMENT OF FUCH’S:– Hypertonic solutions – BCL– Lubricants– Lower IOP– Conjunctival flap– Corneal transplantation: PK/ DSEK

CHEDCHED1:First two years of lifephotophobia and tearingnystagmus is absent

CHED2:At birthDiffuse ground glass appearanceNystagmusDeafness

POSTERIOR POLYMORPHOUS DYSTROPHY

HISTOPATHOLOGY

LATTICE DYSTOPHY/ AMYLOID/ PINK AMORPHOUS/ CONGO RED/APPLE GREEN BIREFRINGENCE

GRANULAR DYSTOPHY/ HYALINE/ MASSON TRICHROME - RED

MACULAR DYSTOPHY/ MPS/ ALCIAN BLUE

SPECULAR MICROSCOPY

CORNEAL GUTTAE

CONFOCAL MICROSCOPY

Images of a normal cornea obtained using the HRT III

Confocal microscopy in EBMD

AS-OCT

• Diagnosis – Corneal Imaging– Corneal measurements

• Management: Treatment planning– Refractive surgery

PACHYMETRY

• Measurement of cornea thickness • Indirect measurement of the endothelial

pump function• Central corneal thickness greater than the

thickness in the mid-peripheral suspect endothelial dysfunction

MANAGEMENT

Topical treatment• Hyperosmotics• Lubricants• Steroids

Contact lenses:• Soft lenses for recurrent erosions• Regression of Lisch epithelial corneal dystrophy• High-Dk soft lenses – ruptured bullae in endothelial dystrophies• RGP lenses for visual rehabilitation• Scleral lenses for both

Long-term follow up of autologous serum treatment for recurrent corneal erosions

Clinical & Experimental Ophthalmology 38(7): 683–687 2010

SURGICAL MANAGEMENT

• ANTERIOR STROMAL PUNCTURE

ASP-Nd:YAG laser

Human cornea treated at 2.0-2.5 mJ. Precise vertical cutpenetrates to base of Bowman's layer (X1600)

Ref: Invest Ophthalmol Vis Sci 31:1555-1559, 1990

• EPITHELIAL DEBRIDEMENT

PHOTOTHERAPEUTIC KERATECTOMY

PTK

Adjunctive Rx:

• Debridement• MMC

KERATOPLASTY

MOLECULAR GENETICS

• Better understanding of the disease process• Identification of overlapping and atypical

cases• Precise classification for treatment planning• Identification of carrier status – genetic

counselling

GENES IMPLICATED IN CD• TGFb-1

– EBMD– Thiel-Behnke– Granular– Lattice

• GELSOLIN GENE– Meretoja(Lattice type II)

• TACSTD2 GENE (TUMOR-ASSOCIATED CALCIUM SIGNAL TRANSDUCER 2)– Gelatinous drop like corneal dystrophy (GDLD)

• KRT3 AND KRT12 GENES– Meesmann’s

• CHST6 (CARBOHYDRATE 6-SULFOTRANSFERASE) GENE– Macular dystrophy

• COL8A2– Fuch’s

Corneal Dystrophies in India

• Autosomal dominant TGFBI related dystrophies: North India

• Autosomal recessive CHED and MCD: South India

GENETIC COUNSELLING

• Autosomal dominant inheritance• Critical if the prognosis is guarded:– Meesmann's– Reis-Buckler's– Granular– Lattice

GENE THERAPY

• Direct observation of the target tissue in vivo• Immune-privileged• Topical/ intrastromal/ intracameral gene delivery• Corneal transplantation– Ex vivo gene transfer – Modulation in the donor cornea prior to

transplantation– Reduces

• Immunogenicity • Recurrence in donor cornea

• Contralateral eye - control

RECAP

“What’s hardest of all? It’s what you think is

easiest: to see with your eyes what’s before your eyes.”

- Johann Wolfgang von Goethe

Thank you