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.

• 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.

Iris atrophy, corectropia, and pseudopolycoria

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

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.

Congenital bulging enlargement of the anterior segment with thinning and clouding of the cornea and anterior sclera. Iris is

adherent to opacified cornea.

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.

The corneal opacities, are identifiable as small flakes and spots and were present throughout the entire stromal thickness.

POSTERIOR AMORPHOUS CORNEAL DYSTROPHY

Posterior Amorphous Corneal Dystrophy• Rare autosomal dominant stromal

dystrophy is bilaterally symmetric.• Appears early in life and may be

congenital

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

A markedly opaque cornea due to stromal edema secondary to defective endothelial cells

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

• 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 color because 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 FindingsHistopathologic examination reveals:• Thick collagenase bundles haphazardly

arranged, with focal areas of myofibroblastic proliferation.

Clinically corneal keloids appear as gray-white elevatedmasses diffusely involving the entire stroma or as localized

solitary nodules.

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

Haab’s striae

Horizontal or concentric, single or multiple, parallel lines in the cornea caused by tears in Descemet’s membrane

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

Corectopia and ectropion uvea with minimal stromal iris atrophy

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

Extensive iris atrophy with polycoria and ectropion uvea in a patient with progressive iris atrophy

Cogan-Reese (Iris-nevus) Variant

Clusters of pigmented iris nodules occurred only in the areas that appeared hypochromic

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.

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).