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 13.016.5 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.