Congenital Disorders of the Cornea

Anomalies of Size and Shape of the Cornea

• Microcornea• Megalocornea• Cornea plana

MICROCORNEA

Microcornea

• clear cornea of normal thickness • diameter is < 10 mm (or 9 mm in a newborn)

• Anterior microphthalmos – whole anterior segment is small

• Microphthalmos– entire eye is small and malformed

• Nanophthalmos– eye is small but otherwise normal

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 & ↑ 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

Megalocornea

• Bilateral, nonprogressive corneal enlargement• X-linked recessive • Histologically normal cornea measuring 13.0-

16.5 mm in diameter• Males are more typically affected, but

heterozygous women may demonstrate a slight increase in corneal diameter.

Pathogenesis

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

• Arrested buphthalmos and exaggerated growth of the cornea in relation to the rest of the eye

Clinical Findings

Associated ocular anomalies:• Iris translucency (diaphany)• Miosis• Goniodysgenesis• Cataract• Ectopia lentis• Arcus juvenilis• Mosaic corneal dystrophy • Glaucoma

Associated systemic conditions:• Craniosynostosis• Frontal bossing• Hypertelorism• Facial anomalies• 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

CORNEA PLANA

Cornea Plana

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

• Cornal curvature that is the same as the adjacent cornea is pathognomonic

Pathogenesis

• Autosomal recessive and dominant forms of cornea plana have been associated with mutations of the KERA gene (12q22), which codes for keratan sulfate proteoglycans (keratocan, lumican and mimecan)

Clinical Findings

Associated ocular anomalies:• Sclerocornea• Microcornea• Cataracts• Anterior and posterior

colobomas • Hyperopia• Angle-closure glaucoma• Open-angle glaucoma

Associated systemic condition:• Ehlers-Danlos Syndrome

Management

• Refractive errors are corrected • Glaucoma must be controlled either medically

or surgically• Loss of central clarity may indicate

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

Abnormalities of Corneal Structure and/or Clarity

• Posterior embryotoxon• Axenfeld-Rieger syndrome• Peters anomaly• Circumscribed posterior keratoconus• Sclerocornea• Keractasia and congenital anterior staphyloma• Congenital hereditary stromal dystrophy• Posterior amorphous corneal dystrophy• Congenital hereditary endothelial dystrophy

POSTERIOR EMBRYOTOXON

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, and it is visible in 8%-30% of normal eyes as an irregular, opaque ridge 0.5- 2.0 mm central to the limbus.

• Schwalbe’s ring is visible by external examination.

• Usually inherited as a dominant trait

Clinical Manifestations

• Eye is usually normal.

Associated ocular/systemic syndromes:• Allagile syndrome (arteriohepatic dysplasia)• X-linked ichthyosis• Familial aniridia

AXENFELD-RIEGER SYNDROME

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

Axenfeld-Rieger Syndrome

• 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

Peters Anomaly

• Central corneal opacity present at birth that may be associated with variable degrees of iridocorneal adhesion extending from the region of the iris collarette to the border of the opacity.

Peters Anomaly

• 60% bilateral• Associated ocular anomalies present in ~50%

of cases• Associated with systemic malformations in

60% of cases

Clinical Findings

Associated ocular anomalies:• Keratolenticular touch• Cataract• Congenital glaucoma• Microcornea• Aniridia• Persistent fetal vasculature

Associated systemic malformations:

• Developmental delay• Heart defects• External ear abnormalities• Hearing loss• CNS deficits• Spinal defects• Gastrointestinal and

genitourinary defects• Facial clerfts• Skeletal anomalies

Histopathologic Findings

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

Pathogenesis

• Most cases occur sporadically• Autosomal recessive and dominant patterns

• Mutations in the PAX6 gene (11p13), the PITX2 gene (4q25-26), the CYP1B1 gene (2p22-21), or the FOXC1 gene (6p25)

CIRCUMSCRIBED POSTERIOR KERATOCONUS

Circumscribed Posterior Keratoconus

• The presence of a localized central or paracentral indentation of the posterior cornea without any protrusion of the anterior surface, as seen in typical keratoconus.

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 amd/ or amblyopia may occur.

SCLEROCORNEA

Sclerocornea

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

Sclerocornea

• Usually sporadic• Autosomal dominant and recessive patterns• No sex predilection• 90% bilateral• Multiple systemic anomalies have been

reported in association with sclerocornea.

Clinical Findings

• Limbus is usually ill-defined, and superficial vessels that are extensions of normal scleral, episcleral, and conjunctival vessels cross the cornea.

• Cornea plana in 80% (most common associated ocular finding)

• Angle structures commonly malformed

KERATECTASIA AND CONGENITAL ANTERIOR STAPHYLOMA

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

• Intrauterine perforation from an infection or from thinning following secondary failure of neutral crest cell migration results in dermoid transformation of the cornea to stratified squamous epithelium, sparing the eyelids and conjunctiva.

Pathogenesis

• 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.

Clinical Findings

• An opaque, bulging cornea is accompanied by a deep anterior segment.

• Unilateral and sporadic with no familial or systemic association.

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.

CONGENITAL HEREDITARY STROMAL DYSTROPHY (CHSD)

Congenital Hereditary Stromal Dystrophy (CHSD)

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

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

• 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

POSTERIOR AMORPHOUS CORNEAL DYSTROPHY

Posterior Amorphous Corneal Dystrophy

• Gray- white, sheetlike stromal opacities concentrated in the posterior stroma.

• Lesions extend to the limbus• 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 ˚

CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY (CHED)

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 AOG

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 nonbullous epithelial edema• uniform thickening of Descemet’s membrane may be

seen, but no guttae changes are present

CONGENITAL CORNEAL OPACITIES IN HEREDITARY SYNDROMES AND CHROMOSOMAL ABERRATIONS

Congenital Corneal Opacities in Hereditary Syndromes and Chromosomal Aberrations

• Muccopolysaccharidoses (MPS) and mucolipodoses are disorders caused by abnormal carbohydrate metabolism

• Corneal clouding and haziness may be present in the early life in varying degrees in many of this entities, including Scheie syndrome (MPS IS) and Hurler Syndrome (MPS IH).

Secondary Abnormalities Affecting the Fetal Cornea

• Intrauterine keratitis• Congenital corneal keloid• Congenital corneal anesthesia• Congenital glaucoma• Birth trauma• Iridocorneal endothelial syndrome• Arcus juvenalis

INTRAUTERINE KERATITIS: BACTERIAL AND SYPHILITIC

Intrauterine Keratitis: Bacterial and Syphilitic

Maternally transmitted congenital infections can cause ocular damage in several different ways:

• Through direct action of the infecting agent, which damages tissue

• Through a teratogenic effect resulting in malformation

• Through a delayed reactivation of the agent after birth, with inflammation that damages developed tissue.

Clinical Findings

• A posterior corneal defect called von Hippel internal corneal ulcer may follow intrauterine inflammation.

• Often, signs of inflammation may still be present after birth including:– corneal infiltrates and vascularization– keratic precipitates– uveitis

Clinical Findings

• Congenitally acquired syphillis infections caused by the Treponema pallidum spirochete can lead to fetal death or premature delivery.

Clinical Findings

• Interstitial keratitis– can develop in the 1st decade of life in children with

untreated congenital syphilis– rapidly progressive corneal edema followed by

abnormal vascularization in the deep stroma adjacent to Descemet’s membrane

– cornea may assume a salmon pink colorbeacause of intense vascularization (salmon patch)

– blood flow decreases empty ‘ghost’ vessels in the corneal stroma

CONGENITAL CORNEAL KELOID

Congenital Corneal Keloid

• Relatively rare lesions• Commonly described following corneal

perforation or trauma• Bilateral• Described in Lowe disease (oculocerebrorenal

syndrome) and the ACL syndrome (acromegaly, cutis gyrata, cornea leukoma syndrome)

Clinical Findings

Histopathologic examination reveals:• Thick collagenase bundles haphazardly

arranged, with focal areas of myofibroblastic proliferation.

CONGENITAL CORNEAL ANESTHESIA

Congenital Corneal Anesthesia

• Rare and difficult to diagnose• Bilateral• Painless corneal opacities and sterile epithelial

ulcerations during infancy and childhood• Associated with congenital mesenchymal

anomalies, congenital trigeminal hypoplasia and diffuse brainstem anomalies

Management

• Thorough systemic examination:- neuroradiologic studies

• Frequent topical lubrication• Nighttime lid splinting• Lateral tarsorrhaphy

CONGENITAL GLAUCOMA

Congenital Glaucoma

• Primary congenital glaucoma is evident either at birth or within the first few years of life.

• Believed to be caused by dysplasia of the anterior chamber angle without other ocular or systemic abnormalities.

Clinical Findings• Triad of epiphora, photophobia, blepharospasm.• Buphthalmos, with corneal enlargement greater than

12 mm in diameter during the first year of life• Corneal edema is present in 25% of affected infants

at birth and in more than 60% by the 6th month. – May range from mild haze to dense opacification in the

corneal stroma because of elevated IOP.

• Tears in Descemet’s membrane called Haab’s striae may occur acutely due to corneal stretching

BIRTH TRAUMA

Birth Trauma• Progressive corneal edema developing during the first

few postnatal days, accompanied by vertical or oblique posterior striae, may be caused by birth trauma

• Ruptures occur at Descemet’s membrane and the endothelium

• Healing usually takes place, leaving a hypertophic ridge of Descemet’s membrane. The edema may or may not be clear, if it does clear, the cornea can again become edematous at any time later in life.

• High astigmatism and amblyopia may be associated.

IRIDOCORNEAL ENDOTHELIAL SYNDROME

Iridocorneal Endothelial Syndrome

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

• "hammered-silver" appearance of the posterior corneal surface – corneal edema that precluded visualization of the

posterior cornea

"hammered-silver" appearance

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

• Pathology confined to the inner corneal surface: corneal edema may result from the subnormal endothelial pump function (Chandler variant)

Chandler variant

Clinical Findings

• Abnormal endothelium migrates over the anterior chamber angle glaucoma (due to formation of PAS and outflow obstruction)

Clinical Findings

• Abnormal endotheloum spreads onto the surface of the iris contractile membrane iris atrophy, corectopia, polycoria (hallmarks of the essential iris atrophy variant)

• Cogan-Reese (iris-nevus variant)– Multiple pigmented iris nodules

Essential Iris Atrophy Variant

Cogan-Reese (Iris-nevus) Variant

Management

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

successful control of the IOP

ARCUS JUVENILIS

Arcus Juvenilis

• Deposition of lipid in the peripheral corneal stroma, occasionally occurs as a congenital anomaly.

• Involves only a sector of the peripheral cornea and is not associated with abnormalities of serum lipid.

Thank you.