congenital corneal disorders

CONGENITAL ANOMALIES OF CORNEA

Dr. Sneha Thapliyal

Embryology....

• 4-5 weeks: surface ectodermal cells cover the defect primitive corneal epithelium

• Primary acellular stroma or post epithelial layer (random fibrils)

• ~5th week : 1st wave of mesenchymal cells just beneath the primitive epithelium primitive endothelium (double layer)

• ~7th week: 2nd wave b/w endothelium and epi cellular stroma (keratocan)

• 7-10th week: mesenchymal cells differentiate into sclera/cornea + corneal curvature>scleral curvature

• 8th week: endothelium becomes monolayer and starts producing decemets membrane

• 12-26 weeks: epi stratified squamous epi

• 20 weeks: Condensation of acellular anterior stroma bowman’s membrane

• 3rd month: corneal nerves invade stroma

• 5th month: tight junction around endothelial cells

• 5-7th month: transparent in utero

Na-k ATP pump

CORNEA •Forms the anterior 1/6th of the globe•DIA: H 11.5-12, V 10.5-11

•CURVATURE:Anterior: 7.8mm;Posterior: 6.5mm

•REFRACTIVE POWER:43D

•CORNEAL THICKNESS:Central: 0.52mmPeripheral: 0.67mm

LAYERS OF CORNEA

EPITHELIUM

INTER CELLULAR JUNCTIONS•DESMOSOMES•ADHERENS JUNCTIONS•TIGHT JUNCTIONS•GAP JUNCTIONS

CYTOPLASMIC FILAMENTS•KERATIN•ACTIN•MICROTUBULES

SOURCE OF CORNEAL EPITHELIAL CELL:Limbal progenitor epithelial cell k/a adult corneal epithelial cellLocated peripherally in palisades of vogt

BOWMAN’S MEMBRANEAcellular ,forms an interface between basal lamina of epithelium and the lamellar stromaSecreted by both epithelial cells and stromal keratocytesRandomly arranged collagen fibrilsConsiderable resistance to infection and injury.Once destroyed can not regenerateCollagen types:type1 and type 5

STROMA90% thickness of the corneaPredominantly waterStructural network of insoluble and soluble ECM and cellular componentsCELLULAR COMPONENTSCollagenKeratocytesProteoglycans and GAGHistiocytes/wandering macrophagesCorneal nerves

FUNCTIONS OF THE STROMA•Maintain proper curvature

•Mechanical resistance to IOP

•CORNEAL TRANSPARENCY

CORNEAL LAMELLAERandomly arranged in anterior stromaOrthogonal to one another in posterior stroma

ANTERIOR 1/3RD POSTERIOR2/3RD

The type 1 fibrils and corneal lamellae stretch across the cornea from limbus to limbus in a belt like fashion where they turn and for a circumferential annulus 1-2.5mm wide around the cornea maintaining the curvature of the cornea

PROTEOGLYCANSCORE PROTIENDECORINLUMICANKERATOCANMIMECAN

Attached covalently to GAG’SNon covalently to collagen fibrils

FUNCTIONS•Tissue volume•Maintain the spatial order of collagen fibrills•Resist compressive forces•Viscoelastic properties to tissue

GAG:•Keratan sulphate (60%) posterior stroma•Dematan sulphate (40%) anterior stroma

KERATOCYTES

•Are fibroblasts found through out stroma

•Are active in neonatal life and during trauma

•Large nucleus and less cell organelles

•KERATOCYTE PROGENITOR CELLS subpopulation of adult stromal stem cell present in periphery near the limbus

DUA’S LAYER•Also known as pre descemets layer•Simulating DALK air bubbles were injected into the cornea after descemets membrane was surgically removed•It formed two types of air bubbles type 2 which dissipated and type 1 which did not.•Further experiments showed that all air bubble free specimens could be reinflated with a type 1 bubble•Indicating bubble was being trapped by a distinct layer of material which is not a normal variation of corneal stroma•Results were studied by optical and electron microscopy that revealed a thin layer of corneal collagen between corneal stroma and descemets membrane

DESCEMET’S MEMBRANE•Anterior banded zone is present at birth•Posterior 2/3rd is the non banded zone formed by endothelium•Regenerates post trauma•Highly elastic•Consists of collagen type4 ,laminin, fibronectin and collagen type 8•Schwalbe’s line•Hassel henle bodies •Guttae

ENDOTHELIUM•Single layer of flat polygonal cells•Hexagonal cells attached to descemet’s membrane via hemidesmosomes and to each other by desmosomes•Metabolically active with abundant granules•6000 at birth falls by 26% in 1st year falls by 26% in next 11 yearsstable, 2400-3000cells/sqmm•Polymegathism•70-80%cells are hexagonal if not is none as pleomorphism

BLOOD SUPPLY•AVASCULAR•Small loops derived from anterior cilliary vessels that invade periphery for about 1mm and provide nourishment

CORNEAL NERVES

Congenital anomalies of cornea.....

Congenital anomalies

1. Anomalies of size and shape2. Mesenchymal dysgenesis of anterior

ocular segment- anterior cleavage syndrome

3. Corneal dystrophies

Developmental corneal anomalies of size and shape

• Absence of the cornea• Anomalies of corneal size• Anomalies of corneal shape

Absence of cornea

• True absence• True cryptophthalmos/ablepharon• Pseudocryptophthalmos

True absence

• Very rare• Always accompanied by agenesis of

various other anterior segment structures

Cryptophthalmos • AR, B/L• Skin (dermoid

transformation) replaces normal eyelid architecture

• Connect to the underlying globe and anterior segment grossly abnormal

• Absence of lashes, brows, lacrimal gland and cannaliculi

• Small or absent AC

Diagnostic criteria for cryptophthalmos syndrome

FRASER SYNDROMEMajor criteria Minor criteria

1. Cryptophthalmos2. Synctactyly3. Abnormal genital 4. Sibling with cryptophthalmos

syndrome

1. Congenial malformation of the nose 2. Congenital malformation of the ears3. Congenital malformation of the larynx4. Cleft lip and/or palate5. Skeletal defects6. Umbilical hernia7. Renal agenesis 8. Mental retardation

Atleast 2 major criteria and one minor criteria or one major and 4 minor criteria

Pseudocryptophthalmos

• Total ankyloblephron• Eyelids form but fail to separate• Normal cornea and conjunctiva covered by

skin• Both lashes and brows are present• Vision restored by surgery creating a

palpebral fissure

Anomalies of Size

Microcornea�

Megalocornea�

Microcornea Clear cornea of normal thickness

H Diameter is < 10 mm (or 9.5-10 mm in a newborn 10-12.5 MM IN ADULTHOOD)

Non progressive, u/l or b/l, no sex predilection� Anterior microphthalmos: whole anterior segment is small� Microphthalmos: entire eye is small and malformed

Nanophthalmos: eye is small but otherwise normal MIDAS: DELETION OF SHORT ARM OF X P 22 MICRO+ DERMA APLASIA+ SCLEROCORNEA

Pathogenesis

• Cause unknown�• Fetal arrest of growth of the cornea in the

5th month• Overgrowth of the anterior tips of the optic �

cup, which leaves less space for the cornea to develop.

Clinical Findings

• Autosomal dominant or recessive�• Equal sex predilection• Cornea relatively flat: hyperopia & �

increased incidence of angle-closure glaucoma

Clinical Findings Associated ocular anomalies:• Persistent fetal vasculature�• Congenital catarcts�• Anterior segment dysgenesis�• Optic nerve hypoplasia�

Associated systemic conditions:• Myotonic dystrophy�• Fetal alcohol syndrome�• Achondroplasia�• Ehlers-Danlos syndrome�

Management

• Excellent visual prognosis if an isolated �finding

• Spectacles to treat the hyperopia resulting �from the flat cornea

• Specific treatment for concurrent ocular �pathology

Megalocornea

• Bilateral, nonprogressive �corneal enlargement

• X-linked recessive�• Histologically normal cornea �

measuring >=12MM AT BIRTH AND AFTERV 2 YRS >13.0 mm

• Males are more typically �affected

Pathogenesis

• �Failure of the optic cup to grow and of its anterior tips to close, leaving a larger space for the cornea to fill

Three patterns

1. Simple megalocornea2. Anterior megaophthalmos3. Buphthalmos

Simple megalocornea

• Normal cornealdiameter >13mm• Non progressive• AD inheritance

Anterior megaophthalmos• X linked recessive• Central cornea usually clear but may contain

mosaic stromal opacity• Corneal curvature is normal • Deep anterior chamber• Hypoplastic iris stroma• Excess mesenchymal tissue in angle

increased IOP• Lens subluxation and cataracts before 40 years

Buphthalmos • Triad of: haab’s striae, increaesd IOP and

optic disk changes• Milder case can be differentiated by

sharply demarcated limbal region seen in megalocornea

• A-scan : to measure axial length in which entire globe is increased along with cornea

Clinical Findings Associated ocular anomalies:

• Iris translucency (diaphany)• Miosis�• Goniodysgenesis�• Cataract�• Ectopia lentis�• Arcus juvenilis�• Mosaic corneal dystrophy�• Glaucoma�• Craniosynostosis• Frontal bossing�• Hypertelorism�• Facial anomalies�

Associated systemic conditions �

• Dwarfism• Facial hemiatrophy�• Mental retardation�• Hypotonia�• Down Syndrome�• Marfan Syndrome�• Alport Syndrome�• Osteogenesis imperfecta�• Mucolipidosis type II

Management• Intraocular pressure testing and slit lamp

biomicroscopy : to rule out congenital glaucoma�• Ultrasonography: to determine short vitreous

length , deep lens and iris position, and normal axial length that distinguish megalocornea from buphthalmos caused by congenital glaucoma

�• Careful cataract surgery: to implant the IOL in the

lens capsular bag

Anomalies of shape of cornea

1. Cornea plana/sclerocornea2. Posterior keratoconus:

generalized/circumscribed3. Keratoglobus4. Congenital staphyloma and keratectasia

Cornea Plana

• Flat cornea, where the radius of �curvature is less than 43 D, and readings of 30-35D are common

• Corneal curvature that is the �same as the adjacent cornea is pathognomic

• All cases have some degree of peripheral or central scleralization

Sclerocornea

• Nonprogressive, noninflammatory �scleralization of the cornea, may be limited to the corneal periphery, or the entire cornea may be involved.

Pathogenesis• Autosomal recessive and dominant forms �

of cornea plana and sclerocornea, AR having more severe manifestation

• 7th-8th gestational weeks when mesenchymal cells differentiate into sclera and cornea and also allows corneal curvature to exceed scleral curvature.

Clinical Findings Associated ocular anomalies:

• Sclerocornea�• Microcornea�• Cataracts�• Anterior and posteriorcolobomas�• Hyperopia�• Angle-closure glaucoma�• Open-angle glaucoma�

Associated systemic condition:• Ehlers-Danlos Syndrome�

Management

• Refractive errors are corrected�• Loss of central clarity may indicate �

penetrating keratoplasty, but cornea plana increases the risk of graft rejection and post keratoplasty glaucoma.

Generalized posterior keratoconus

• Increased posterior corneal curvature with a short radius of curvature

• Normal anterior corneal surface• Central cornea is thinned but clear• Sporadic as a result of developmental

arrest.• Less common

Circumscribed Posterior Keratoconus

• More common�• Localized central or

paracentral indentation of the posterior cornea without any protrusion of the anterior surface, as seen in typical keratoconus

Pathogenesis• Abnormal migration of the 2nd wave of

mesenchymal cells that normally form corneal stroma

• Represent mild variant of Peter’s anomaly therefore implying some intrauterine inflammation or anterior segment dysgenesis

Clinical Findings• �Variable amount of overlying stromal haze• Loss of stromal substance can lead to � corneal

thinning approaching one third of normal.• �Descemet’s membrane and endothelium are

usually present in the area of defect• Focal deposits of � pigmentation and guttae are

often present at the margins of opacity.• Astigmatism and/ or amblyopia may occur�

Keratectasia and Congenital Anterior Staphyloma

• �Unilateral conditions that are both characterized by protrusion of the opaque cornea between the eyelids at birth.

• Differ only in the presence �of a uveal lining of the cornea in congenital anterior staphyloma

Pathogenesis

• �Secondary failure of neutral crest cell migration results in dermoid transformation of the cornea to stratified squamous epithelium, sparing the eyelids and conjunctiva.

• Histopathologically, � Descemet’s membrane and endothelium are absent, and a uveal lining is present (except in keratectasia).

• The cornea is variably � thinned and scarred and the anterior segment disorganized, with the lens occasionally adherent to the posterior cornea, resembling unilateral

Peters anomaly

Management

• Except in very mild cases, � visual prognosis is poor because of associated severe damage to the anterior segment.

• Penetrating keratoplasty is rarely warranted, and enucleation may be required for a blind, glaucomatous, painful eye

Keratoglobus

• b/l, non inflammatory • Entire cornea is thinned out ( 1/3rd-1/5th the

normal thickness) and takes globular shape

• Keratomertry readings: 60-70 D• Strong association with Ehler-Danlos

syndrome type VI

Histopathology • Absent/fragmented Bowman’s membrane• Thinned stroma with normal lamellar

orientation• Thin Decemet’s membrane with focal

breaks• Normal endothelium• Thin sclera

Clinical features• Globular shape of

cornea• Thinning more

pronounced in mid-periphery

• Very deep anterior chamber

• Otherwise normal anterior segment structures

Management• Spectacle correction for high myopia to

avoid amblyopia.• 2 stage procedure: epikeratplasty or

tectonic lamellar corneo-scleral graft followed by penetrating keratoplasty weeks to months later

• Protective eye wear is strongly encouraged and enforced.

Anterior chamber cleavage syndrome

• Posterior embryotoxon• Axenfeld-Rieger syndrome• Peter’s anomaly• Iridogoniodysgenesis

Posterior Embryotoxon• �Thickened and centrally

displaced anterior border ring of Schwalbe

• Schwalbe’s ring �represents the junction of the trabecular meshwork with the termination of Descemet’s membranes.

• Usually inherited as a �dominant trait

Axenfeld-Rieger Syndrome• �Represents a spectrum of

disorders characterized by an anteriorly displaced Schwalbe’s ring (posterior embryotoxon), with attached iris strands, iris hypoplasia, and glaucoma in 50% of the cases occurring in late childhood or adulthood

• Associated skeletal, cranial, facial, and dental abnormalities are often present

• Transmission is usually dominant (75%) for the

Axenfeld-Rieger group, but it can be sporadic.

• Spectrum of mutations of �transcription factors located in chromosome region 6p25, known as

forkhead genes, are responsible for many developmental defects of the anterior chamber of the eye

Peters Anomaly• 3 anatomic components �1. Central posterior

corneal defect in endo and DM with overlying corneal opacity

2. Keratoiridial adhesion3. Corneaolenticular

contact or cataract

• Defective neural crest cell migration in 6th-8th week of gestation.

• 80% bilateral�• Inheritance is mostly sporadic• Associated ocular anomalies present in �

~50%of cases• Associated with systemic malformations

in60% of cases

Clinical FindingsAssociated ocular

anomalies:�• Keratolenticular touch• Cataract�• Congenital glaucoma�• Microphthalmos�• Aniridia�• Persistent fetal vasculature�

Associated systemic malformations

• craniofacial anomalies�• External ear abnormalities�• Hearing loss �• Peter’s plus’: short-limbed �

dwarfism, cleft lip/palate,learning difficulties

Histopathologic Findings

• Localized absence of the corneal endothelium and Descemet’s membrane beneath the area of opacity

Corneal Dystrophies

• Congenital hereditary stromal dystrophy�• Posterior amorphous corneal dystrophy�• Congenital hereditary endothelial �

dystrophy

Congenital Hereditary Stromal Dystrophy (CHSD)

• Extremely rare � AD stationary dystrophy presents at birth with bilateral central superficial corneal clouding.

• Anterior corneal stroma exhibits an ill-defined flaky or feathery opacity.

�• Cornea is clear peripherally�• No edema, photopobia or tearing,

but the opacities can be sufficiently dense to cause a reduction in vision

Posterior Amorphous Corneal Dystrophy

• �Rare autosomal dominant stromal dystrophy is bilaterally symmetric.

• Appears early in life and may be congenital

• Grouped vesicles, refractile geographic lesions, scalloped bands and peripheral iridocorneal adhesions

• Gray-white, sheet like stromal opacities concentrated in �the posterior stroma.

• Epithelium appears normal, but Descemet’s �membranes shows involvement, with focal areas of endothelial disruption

• Central corneal thinning�• Hyperopia�• Flattened corneal topography�• Anterior iris abnormalities�• Fine iris process extending to Schwalbe’s line for 360 �

degree.

Congenital hereditary endothelial dystrophy (CHED)

• A cause � of bilateral congenital corneal edema• Due � to primary dysfunction of the corneal

endothelium, characterized by increased permeability and abnormal Descemet’s membrane secretion

• No consistent associations with other systemic �abnormalities

• Dominant form (CHED 1)• Presents in the first or second year of life�• Slowly progressive�• Accompanied by pain, photophobia, and tearing but �

nystagmus is not present• Cornea exhibits a diffuse, blue-gray, ground-glass �

appearance• Primary abnormality: � degeneration of endothelial

cells during or after the 5th month

• Autosomal Recessive Type(CHED 2)

• Presents at birth, remains stationary �and

• Accompanied by nystagmus• Bluish white cornea may be 2-3 �

times normal thickness and have a ground-glass appearance, but this finding is not associated with tearing or photopobia

• Diffuse non bullous epithelial edema�• �Uniform thickening of Descemet’s

membrane may be seen, but no guttae changes are present

Iridocorneal Endothelial Syndrome

• Spectrum of disorders characterized by varying �degrees of corneal edema, glaucoma and iris abnormalities

• Corneal edema that precluded visualization of the posterior cornea

Pathogenesis

• Unknown but appears to involve an � abnormal clone of endothelial cells that takes on ultrastructural characteristics of epithelial cells

• Varying degrees of � endothelialization take place in the anterior chamber angle and on the iris surface.

Clinical Findings• Iris atrophy, corectopia,

polycoria (hallmarks of the essential iris atrophy variant)

• Cogan-Reese (iris-nevus variant)

• Chandler variant: hammered silver endothelium

Management

• Penetrating keratoplasty�• Long-term graft clarity depends on the �

successful control of the IOP

congenital corneal disorders

Education